Amide-containing compound having improved solubility and method of improving the solubility of an amide-containing compound

ABSTRACT

The present invention is directed to novel amide-containing compounds which have an improved solubility and a method of improving the solubility of amide-containing compounds. The amide-containing compounds include oxazolidinone compounds and the bioavailability of these oxazolidinone compounds is improved by improving the solubility thereof.

FIELD OF THE INVENTION

[0001] The present invention is directed to amide-containing compounds having an improved water solubility and a method for improving the water-solubility of amide-containing compounds in general and, specifically, to oxazolidinone compounds having improved water solubility and a method of improving the water-solubility of oxazolidinone compounds.

BACKGROUND OF THE INVENTION

[0002] There are many compounds that contain amide groups which have desirable pharmacological activity. For example, oxazolidinone derivatives containing an amide group are known to exhibit a variety of biological activities.

[0003] Oxazolidinone derivatives have been shown to be inhibitors of monoamine oxidase-B, an enzyme implicated in Parkinson's disease. Ding et al., J. Med. Chem. 36:3606-3610 (1993).

[0004] Scientists have reported that certain oxazolidinone derivatives exhibit beneficial antibacterial effects. For instance, N-[3-[3-fluoro-4-(morpholin-4-yl)phenyl]2-oxooxazolidin-5(s)-ylmethyl]acetamide (below) has been reported to be useful for the treatment of bacterial infections. Lizondo et al., Drugs of the Future, 21:1116-1123 (1996).

[0005] A ten step synthesis of oxazolidinone antibiotics has been described in U.S. Pat. No. 5,547,950. A four step synthesis of the antibacterial compound U-100592 also has been reported. Schauss et al., Tetrahedron Letters, 37:7937-7940 (1996). A five step preparation of enantiomerically pure cis- and trans-N-(propionyl)hexahydrobenzoxazolidin-2-ones further was reported in De Parrodi et al., Tetrahedron: Asymmetry, 8:1075-1082 (1997).

[0006] The synthesis of the oxazolidinone antibacterial agent shown below has been reported. Wang et al., Tetrahedron, 45:1323-1326 (1989). This oxazolidinone was made using a process that included the reaction of an aniline with glycidol to provide an amino alcohol, and the diethylcarbonate mediated cyclization of the amino alcohol to afford an oxazolidinone.

[0007] The synthesis of oxazolidinone antibacterial agents, including the compound shown below has been reported. U.S. Pat. No. 4,705,799. The process used to make the compound shown below included a metal mediated reduction of a sulfonyl chloride to provide a sulfide.

[0008] The synthesis of oxazolidinone antibacterial agents, including the pyridyl compound shown below has been reported. U.S. Pat. No. 4,948,801. The process used included an organometallic mediated coupling of an organotin compound and an aryl iodide.

[0009] U.S. Pat. No. 5,652,238 discloses carboxylic and phosphate esters of substituted-hydroxyacetyl piperazine phenyl oxazolidinones.

[0010] U.S. Pat. No. 5,688,792 discloses substituted oxazine and thiazine oxazolidinone useful as antibacticals.

[0011] PCT International Publication WO 98/54161 discloses oxazolidinone antibacterial agents having a thiocarbonyl functionality.

[0012] U.S. Pat. No. 5,968,962 and PCT International Publication WO 99/29688 discloses phenyloxazolidinones having a C—C bond to 4-8 membered heterocyclic rings.

[0013] U.S. Pat. No. 5,952,324 discloses bicyclic oxazine and thiazine oxazolidinone useful as antibacticals.

[0014] PCT publications, WO 99/64416, WO 99/64417, and WO 00/21960 disclose oxazolidinone derivatives useful as antibacterial agents.

[0015] PCT Publication, WO 00/10566 discloses isoxazolinones useful as antibacterial agents.

[0016] U.S. Pat. No. 5,880,118 discloses substituted oxazine and thiazine oxazolidinone antimocrobials.

[0017] U.S. Pat. No. 6,968,962 discloses phenyloxazolidinones having a C—C bond to 4-8 membered heterocyclic rings.

[0018] U.S. Pat. No. 5,981,528 discloses antibiotic oxazolidinone derivatives.

[0019] U.S. Patent application Serial No. 60/236,595 discloses N-({(5S)-3-[4-(1,1-dioxido-4-thiomorpholinyl)-3,5-difluorophenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide.

[0020] PCT publications, WO 99/64416, WO 99/64417, and WO 00/21960 disclose isoxazolinone derivatives useful as antibacterial agents.

[0021] PCT publication, WO 00/10566 discloses isoxazolinones useful as antibacterial agents.

[0022] U.S. Pat. No. 5,164,510 discloses 5′-indolinyloxazolidin-2-ones of formula XI

[0023] which are useful as antibacterial agents.

[0024] U.S. Pat. Nos. 5,036,092; 5,036,093; 5,039,690; 5,032,605 and 4,965,268 disclose aminomethyl oxazolidinyl aza cycloalkylbenzene derivatives useful as antibacterial agents.

[0025] U.S. Pat. Nos. 5,792,765 and 5,684,023 disclose substituted isoxazolinones useful as antibacterial agents.

[0026] International Publication No. WO 97/09328 discloses phenyloxazolidinones having a C—C bond to 4-8 membered heterocyclic rings useful as antimicrobial agents.

[0027] PCT International Publication WO 93/23384 discloses oxazolidinones containing a substituted diazine moiety and their use as antimicrobials.

[0028] PCT International Publication WO 95/07271 discloses substituted oxazine and thiazine oxazolidinones and their use as antimicrobials.

[0029] However, even though some amide-containing compounds have been shown to be extremely effective in the treatment of certain physiological disorders, some of these compounds have a low bioavailability due to their low water solubility and/or low permeability through biological barriers, such as the blood brain barrier and the intestinal barrier.

[0030] In order to increase the bioavailability of certain amines, peptides and peptidomimetics, prodrugs of these compounds, have been proposed. Zheng et al, Tetrahedron Letters, 55:4237-4254 (1999), Wang et al, Journal of Controlled Release, 65:245-251 (2000) and Wang et al, Bioorganic & Medicinal Chemistry, 6:417-426 (1998). These prodrugs derivatize certain polar functional groups transiently and bioreversably to mask undesirable physical chemical characteristics of the groups without permanently altering the pharmacological properties of the molecules and have been used very successfully in cases where the prodrug derivatization involves converting a carboxyl or a hydroxyl functional group into an ester which can be readily hydrolyzed in vivo either chemically or enzymatically. However, this strategy has not been successfully used in the case of an amide group due to the chemical stability thereof.

[0031] As such, there is a need for amide-containing compounds having an improved water-solubility and bioavailability and for methods for synthesizing these compounds.

SUMMARY OF THE INVENTION

[0032] The objects of the present invention are met by providing an oxazolidinone derivative of Formula (I)

[0033] wherein J is O or S;

[0034] R₂₁₀ is

[0035] R₃₁₀, R₄₁₀ and R₅₁₀ each independently are

[0036] a) H,

[0037] b) C₁₋₄ alkyl,

[0038] c) halogen,

[0039] d) C₁₋₄ alkoxy,

[0040] e) hydroxy,

[0041] f) (CH₂)_(c)OP(O)(OH)₂,

[0042] g) C₁₋₄ acyloxy, or

[0043] h) C₁₋₄ alkyl substituted by halogen, hydroxy, acyloxy, NR₁₂₁₀R₁₃₁₀, or alkoxy;

[0044] R₆₁₀, R₇₁₀ and R₈₁₀ each independently are

[0045] a) H,

[0046] b) CH₃, or

[0047] c) C₂H₅;

[0048] R₉₁₀ and R₁₀₁₀ each independently are

[0049] a) H,

[0050] b) CH₃,

[0051] c) C₂H₅, or

[0052] d) combine to form a C₃₋₅ cycloalkyl;

[0053] R₁₁₁₀ is H or C₁₋₆ alkyl;

[0054] R₁₂₁₀ and R₁₃₁₀ each independently are

[0055] a) H,

[0056] b) C₁₋₄ alkyl, or

[0057] c) combine to form a heterocyclic ring;

[0058] wherein a is 0 or 1, b is 0 or 1, and c is 0 or 1, with the proviso that when Q′ is

[0059]  b is 0 and a+b is 0 or 1;

[0060] R₁ is

[0061] a) C₁₋₄ alkyl,

[0062] b) C₂₋₄ alkenyl,

[0063] c) OC₁₋₄ alkyl,

[0064] d) C₃₋₆ cycloalkyl,

[0065] e) C₁₋₄ alkyl substituted with 1-3F, 1-2Cl, CN, —COOC₁₋₄ alkyl or a C₃₋₆ cycloalkyl; or

[0066] f) H

[0067] A is

[0068] R₄ is

[0069] a) C₁₋₄ alkyl optionally substituted with one or more halos, OH, CN, NR₁₀R₁₁, or —CO₂R₁₃,

[0070] b) C₂₋₄ alkenyl,

[0071] c) —NR₁₆R₁₈,

[0072] d) —N₃,

[0073] e) —NHC(═O)R₇,

[0074] f) —NR₂₀C(═O)R₇,

[0075] g) —N(R₁)₂,

[0076] h) —NR₁₆R₁₉, or

[0077] i) —NR₁₉R₂₀,

[0078] R₅ and R₆ at each occurrence are the same or different and are

[0079] a) C₁₋₂ alkyl, or

[0080] b) R₅ and R₆ taken together are —(CH₂)_(k)—;

[0081] R₇ is C₁₋₄ alkyl optionally substituted with one or more halos;

[0082] R₁₀ and R₁₁ at each occurrence are the same or different and are

[0083] a) H,

[0084] b) C₁₋₄ alkyl, or

[0085] c) C₃₋₈ cycloalkyl;

[0086] R₁₃ is

[0087] a) H, or

[0088] b) C₁₋₄ alkyl;

[0089] R₁₄ and R₁₅ at each occurrence are the same or different and are

[0090] a) C₁₋₄ alkyl, or

[0091] b) R₁₄ and R₁₅ taken together are —(CH)_(l)—;

[0092] R₁₆ is

[0093] a) H,

[0094] b) C₁₋₄ alkyl, or

[0095] c) C₃₋₈ cycloalkyl;

[0096] R₁₇ is

[0097] a) C₁₋₄ alkyl, or

[0098] b) C₃₋₈ cycloalkyl;

[0099] R₁₈ is

[0100] a) H,

[0101] b) C₁₋₄ alkyl,

[0102] c) C₂₋₄ alkenyl,

[0103] d) C₃₋₄ cycloalkyl,

[0104] e) —OR₁₃ or

[0105] f) —NR₂₁R₂₂;

[0106] R₁₉ is

[0107] a) Cl,

[0108] b) Br, or

[0109] c) I;

[0110] R₂₀ is a physiologically acceptable cation;

[0111] R₂₁ and R₂₂ at each occurrence are the same or different and are

[0112] a) H,

[0113] b) C₁₋₄ alkyl, or

[0114] c) —NR₉₁R₂₂ taken together are —(CH₂)_(m)—;

[0115] wherein R₂₃ and R₂₄ at each occurrence are the same or different and are

[0116] a) H,

[0117] b) F,

[0118] c) Cl,

[0119] d) C₁₋₂ alkyl,

[0120] e) CN

[0121] f) OH,

[0122] g) C₁₋₂ alkoxy,

[0123] h) nitro, or

[0124] i) amino;

[0125] Q is

[0126] m) a diazinyl group optionally substituted with X and Y,

[0127] n) a triazinyl group optionally substituted with X and Y,

[0128] o) a quinolinyl group optionally substituted with X and Y,

[0129] p) a quinoxalinyl group optionally substituted with X and Y,

[0130] q) a naphthyridinyl group optionally substituted with X and Y,

[0131] Q and R₂₄ taken together are

[0132] wherein Z¹ is

[0133] a) —CH₂—,

[0134] b) —CH(R¹⁰⁴)—CH₂—,

[0135] c) —C(O)—, or

[0136] d) —CH₂CH₂CH₂—;

[0137] wherein Z² is

[0138] a) —O₂S—,

[0139] b) —O—,

[0140] c) —N(R¹⁰⁷)—,

[0141] d) —OS—,

[0142] e) —S—, or

[0143] f) S(O)(NR₁₉₀);

[0144] wherein Z³ is

[0145] a) —O₂S—,

[0146] b) —O—,

[0147] c) —OS—,

[0148] d) —S—, or

[0149] e) S(O)(NR₁₉₀)

[0150] wherein A¹ is

[0151] a) H—, or

[0152] b) CH₃;

[0153] wherein A² is

[0154] a) H—,

[0155] b) HO—,

[0156] c) CH₃—,

[0157] d) CH₃O—,

[0158] e) R¹⁰²O—CH₂—C(O)—NH—

[0159] f) R¹⁰³O—C(O)—NH—,

[0160] g) (C₁-C₂)alkyl-O—C(O)—,

[0161] h) HO—CH₂—,

[0162] i) CH₃O—NH—,

[0163] j) (C₁-C₃)alkyl-O₂C—

[0164] k) CH₃—C(O)—,

[0165] l) CH₃—C(O)—CH₂—,

[0166] A¹ and A² taken together are:

[0167] wherein R¹⁰² is

[0168] a) H—,

[0169] b) CH₃—,

[0170] c) phenyl-CH₂—, or

[0171] d) CH₃C(O)—;

[0172] wherein R¹⁰³ is

[0173] a) (C₁-C₃)alkyl-, or

[0174] b) phenyl-;

[0175] wherein R¹⁰⁴ is

[0176] a) H—, or

[0177] b) HO—;

[0178] wherein R¹⁰⁶ is

[0179] a) CH₃—C(O)—,

[0180] b) H—C(O)—,

[0181] c) Cl₂CH—C(O)—,

[0182] d) HOCH₂—C(O)—,

[0183] e) CH₃SO₂—,

[0184] g) F2CHC(O)—,

[0185] i) H₃C—C(O)—O—CH₂—C(O)—,

[0186] j) H—C(O)—O—CH₂—C(O)—,

[0187] l) HC≡C—CH₂O—CH₂—C(O)—, or

[0188] m) phenyl-CH₂—O—CH₂—C(O)—;

[0189] wherein R¹⁰⁷ is

[0190] a) R¹⁰²—C(R¹¹⁰)(R¹¹¹)—C(O)—,

[0191] b) R¹⁰³O—C(O)—

[0192] c) R¹⁰⁸—C(O)—,

[0193] f) H₃C—C(O)—(CH₂)₂—C(O)—,

[0194] g) R¹⁰⁹—SO₂—,

[0195] i) HO—CH₂—C(O)—,

[0196] j) R¹¹⁶—(CH₂)₂—,

[0197] k) R¹¹³—C(O)—O—CH₂—C(O)—,

[0198] l) (CH₃)₂N—CH₂—C(O)—NH—,

[0199] m) NC—CH₂—,

[0200] n) F₂—CH—CH₂—, or

[0201] o) R¹⁵⁰R¹⁵¹NSO₂

[0202] p) C(O)CR₁₈₀R₁₈₀R₁₈₁OR₁₈₂,

[0203] q) C(O)CH₂S(O)_(i)CH₃,

[0204] r) C(O)CH₂S(O)(NR₁₈₃)CH₃,

[0205] s) C(S)R₁₈₄,

[0206] t) C(O)CH₂OR₁₈₅,

[0207] u) C(O)(CH₂)C(O)CH₃,

[0208] v) C(O)(CH₂OH)₂CH₃,

[0209] w) C(O)CH₂CH₂OR₁₈₉, or

[0210] x) —CN;

[0211] wherein R¹⁰⁸ is

[0212] a) H—,

[0213] b) (C₁-C₄)alkyl,

[0214] c) aryl —(CH₂)_(p),

[0215] d) ClH₂C—,

[0216] e) Cl₂HC—,

[0217] f) FH₂C—,

[0218] g) F₂HC—,

[0219] h) (C₃-C₆)cycloalkyl, or

[0220] i) CNCH₂—.

[0221] wherein R¹⁰⁹ is

[0222] a) alkylC₁-C₄,

[0223] b) —CH₂Cl

[0224] c) —CH₂CH═CH₂,

[0225] d) aryl, or

[0226] e) —CH₂CN;

[0227] wherein R¹¹⁰ and R¹¹¹ are independently

[0228] a) H—,

[0229] b) CH₃—; or

[0230] wherein R¹¹² is

[0231] a) H—,

[0232] b) CH₃O—CH₂O—CH₂—, or

[0233] c) HOCH₂—;

[0234] wherein R¹¹³ is

[0235] a) CH₃—,

[0236] b) HOCH₂—,

[0237] c) (CH₃)₂N-phenyl, or

[0238] d) (CH₃)₂N—CH₂—;

[0239] wherein R¹¹⁴ is

[0240] a) HO—,

[0241] b) CH₃₀—,

[0242] c) H₂N—,

[0243] d) CH₃O—C(O)—O—,

[0244] e) CH₃—C(O)—O—CH₂—C(O)O—,

[0245] f) phenyl-CH₂—O—CH₂—C(O)—O—,

[0246] g) HO—(CH₂)₂—O—,

[0247] h) CH₃O—CH₂—O— (CH₂)₂—O—, or

[0248] i) CH₃O—CH₂—O—;

[0249] wherein R¹¹⁵ is

[0250] a) H—, or

[0251] b) Cl—;

[0252] wherein R¹¹⁶ is

[0253] a) HO—

[0254] b) CH₃O—, or

[0255] c) F;

[0256] wherein R¹⁵⁰ and R¹⁵¹ are each H or alkyl C₁-C₄ or R¹⁵⁰ and R¹⁵¹ taken together with the nitrogen atom to which each is attached form a monocyclic heterocyclic ring having from 3 to 6 carbon atoms;

[0257] R₁₅₂ is

[0258] a) H,

[0259] b) C₁₋₄alkyl,

[0260] c) C₁₋₄heteroalkyl,

[0261] d) (CH₂)_(l)C(═O)OC₁₋₄alkyl,

[0262] e) (CH₂)_(i)C(═O)C₁₋₄alkyl,

[0263] f) aryl, or

[0264] g) het¹;

[0265] R₁₅₃ and R₁₅₄ are independently

[0266] a) H,

[0267] b) F,

[0268] c) C₁₋₄alkyl,

[0269] d) C₃₋₆cycloalkyl,

[0270] e) C₁₋₄heteroalkyl,

[0271] f) aryl,

[0272] g) het¹,

[0273] h) OC₁₋₄alkyl,

[0274] i) O(C═O)C₁₋₄alkyl,

[0275] j) (C═O)OC₁₋₄alkyl; or

[0276] k) R₁₅₃ and R₁₅₄ taken together are C₃₋₆cycloalkyl;

[0277] R₁₅₅ is

[0278] a) H,

[0279] b) F,

[0280] c) C₁₋₄alkyl,

[0281] d) OC₁₋₄alkyl,

[0282] e) SC₁₋₄alkyl, or

[0283] f) NHC₁₋₄alkyl;

[0284] R₁₅₆ is

[0285] a) H,

[0286] b) C₁₋₄alkyl,

[0287] c) OC₁₋₄alkyl,

[0288] d) SC₁₋₄alkyl, or

[0289] e) NHC₁₋₄alkyl;

[0290] R₁₅₇ is

[0291] a) —H,

[0292] b) —F,

[0293] c) —Cl,

[0294] d) —NH₂,

[0295] e) —OH,

[0296] f) —CN,

[0297] g) —C₁₋₄alkyl,

[0298] h) —OC₁₋₄alkyl,

[0299] i) —C₁₋₄alkyl-W—C₁₋₄alkyl,

[0300] j) —NHC₁₋₄alkyl,

[0301] k) —(CH₂)_(l)C₃₋₆cycloalkyl,

[0302] l) —C(═O)C₁₋₄alkyl,

[0303] m) —OC(═O)C₁₋₄alkyl,

[0304] n) —C(═O)OC₁₋₄alkyl,

[0305] o) —S(O)_(l)C₁₋₄alkyl, or

[0306] p) —C(═O)NHC₁₋₄alkyl;

[0307] R₁₅₈ is

[0308] a) —H,

[0309] b) —CH₃,

[0310] c) —F, or

[0311] d) —OH;

[0312] R₁₅₉ is

[0313] a) —H,

[0314] b) —C₁₋₄alkyl,

[0315] c) —C(═O)C₁₋₄alkyl,

[0316] d) —C(═O)NHC₁₋₄alkyl,

[0317] e) —OC(═O)C₁₋₄alkyl,

[0318] f) —C(═O)OC₁₋₄alkyl, or

[0319] g) —S(O)_(i)C₁₋₄alkyl, or

[0320] h) —C₁₋₄alkyl-W₁—C₁₋₄alkyl;

[0321] R₁₆₀ is H, C₂₋₆ alkenyl, C₂₋₇alkynyl, C₁₋₆ alkyl substituted with one or two of the following:

[0322] a) F,

[0323] b) Cl,

[0324] c) CF₃,

[0325] d) —OH,

[0326] e) C₁₋₄alkoxy,

[0327] f) —CH₂C(═O)C₁₋₄alkyl,

[0328] g) —OC(═O)N(R₁₆₁)₂,

[0329] h) C₁₋₄alkyl S(O)_(n), (wherein n is 0, 1 or 2),

[0330] i) —CN,

[0331] j) carboxy,

[0332] k) —C₁₋₄alkoxycarbonyl,

[0333] l) —C(═O)N(R₁₆₁)₂,

[0334] m) —N(R¹⁶¹)SO₂C₁₋₄ alkyl,

[0335] n) —N(R₁₆₁)C(═O)C₁₋₄ alkyl,

[0336] o) —N(R₁₆₁)C(═O)N(R₄)₂,

[0337] p) —N(R₁₆₁)C(═O)C₁₋₄ alkoxy,

[0338] q) aryl, or

[0339] r) Het₁;

[0340] R₁₆₁ is

[0341] a) H, or

[0342] b) C₁₋₃ alkyl;

[0343] R₁₆₂ is

[0344] a) H,

[0345] b) C₁₋₈ alkyl, optionally substituted with one to three F, Cl, OH, CN, NH₂, OC(═O)C₁₋₄alkyl, or OC₁₋₄ alkyl,

[0346] c) C₃₋₈ alkene, or

[0347] d) C(═O)NR₁₆₃R₁₆₄;

[0348] R₁₆₃ and R₁₆₄ are independently

[0349] a) H, or

[0350] b) C₁₋₈ alkyl, optionally substituted with one to three F, Cl, OH, CN, or NH₂;

[0351] R₁₆₅ is C₁₋₄ alkyl, optionally substituted with 1-3 R₁₆₈;

[0352] R₁₆₆ is

[0353] a) C₁₋₈ alkyl, optionally substituted with 1-3 halo, CN, NO₂, OH, SH or NH₂;

[0354] b) —C(═O)R₁₆₇ or

[0355] c) —C(═S)NHC₁₋₄ alkyl;

[0356] R₁₆₇ is

[0357] a) H,

[0358] b) C₁₋₆ alkyl, optionally substituted with OH, C₁₋₄ alkoxy, NH₂, SH or halo, or

[0359] c) —CH₂OC(═O)C₁₋₄ alkyl;

[0360] R₁₆₈ is

[0361] j) halo,

[0362] k) —CN,

[0363] l) —OH,

[0364] m) —SH,

[0365] n) —NH₂,

[0366] o) —OR₁₆₉,

[0367] p) —NHR₁₆₉,

[0368] q) —N(R₁₆₉)₂, or

[0369] r) —S(═O)_(i)R₁₆₉;

[0370] R₁₆₉ is

[0371] g) C₁₋₆ alkyl,

[0372] h) —C(═O)C₁₋₄ alkyl,

[0373] i) —C(═O)O C₁₋₄ alkyl,

[0374] j) —C(═O)NH₂,

[0375] k) —C(═O)NH C₁₋₄ alkyl, or

[0376] l) —SO₂C₁₋₄ alkyl;

[0377] with the proviso that where j is 0, Y₂ is —CH₂—.

[0378] R₁₇₀ is

[0379] a) H,

[0380] b) C₁₋₁₂ alkyl, optionally substituted with phenyl or CN, or

[0381] c) C₂₋₁₂ alkyl substituted with OH, SH, NH₂, —OC₁₋₆ alkyl, —NHC₁₋₆ alkyl, —NHCOC₁₋₆ alkyl, —NHSO₂C₁₋₆ alkyl, —S(O)_(i)C₁₋₆ alkyl, or one to three halo;

[0382] R₁₇₂ is

[0383] a) H,

[0384] b) C₁₋₈ alkyl,

[0385] c) aryl,

[0386] d) het₁,

[0387] e) C(═W)R₁₇₄,

[0388] f) C(═O)OR₁₇₅, or

[0389] g) S(═O)_(i)R₁₇₆;

[0390] R₁₇₃ is

[0391] a) H, or

[0392] b) C₁₋₈ alkyl;

[0393] R₁₇₄ is

[0394] a) H,

[0395] b) aryl,

[0396] c) het₁,

[0397] d) NR₁₇₇R₁₇₈, or

[0398] e) C₁₋₈ alkyl;

[0399] R₁₇₅ is

[0400] a) C₁₋₈ alkyl,

[0401] b) aryl, or

[0402] c) het₁;

[0403] R₁₇₆ is

[0404] a) aryl,

[0405] b) het₁,

[0406] c) NR₁₇₇R₁₇₈, or

[0407] d) C₁₋₈ alkyl;

[0408] R₁₇₇ and R₁₇₈ are independently

[0409] a) H,

[0410] b) C₁₋₈ alkyl, or

[0411] c) aryl;

[0412] R₁₈₀ and R₁₈₁ taken together form C₃₋₅ cycloalkyl;

[0413] R₁₈₂ is H, CH₃ or C₁₋₄ alkanoyl;

[0414] R₁₈₃ is H, C₁₋₄ alkyl, C₁₋₄ alkanoyl, —C(═O)NH—C₁₋₄ alkyl or —CO₂C₁₋₄ alkyl;

[0415] R₁₈₄ is C₁₋₄ alkyl, CH₂OR₁₈₆, S—C₁₋₄ alkyl, OC₁₋₄ alkyl, or NR₁₈₇R₁₈₈;

[0416] R₁₈₅ is phenyl, —CO₂—(CH₂)₂—OCH₃, —P(═O)(OH)₂, —C(═O)—NR₁₈₇R₁₈₆, or —C(═O)—(CH₂)₂—CO₂H;

[0417] R₁₈₆ is H, phenyl, benzyl, CH₃ or C(═O)CH₃;

[0418] R₁₈₇ and R₁₈₈ are independently H or C₁₋₃ alkyl; or R₁₈₇ and R₁₈₈ taken together form a 5- or 6-membered saturated heterocycle, wherein said saturated heterocycle may further contain one or two additional hetero-atoms selected from a group consisting of O, S(O)_(n) or NR₁₈₂;

[0419] R₁₈₉ is H, CH₃ or benzyl;

[0420] R₁₉₀ is

[0421] a) H,

[0422] b) C₁₋₄ alkyl,

[0423] c) C(═O)C₁₋₄ alkyl,

[0424] d) C(═O)OC₁₋₄ alkyl,

[0425] e) C(═O)NHR₁₉₁, or

[0426] f) C(═S)NHR₁₉₁;

[0427] R₁₉₁ is H, C₁₋₄ alkyl, or phenyl;

[0428] at each occurrence, alkyl in R₁₉₀ and R₁₉₁ is optionally substituted with one or more halo, CN, NO₂, phenyl, C₃₋₆ cycloalkyl, OR₁₉₂, C(═O)R₁₉₂, OC(═O)R₁₉₂, C(═O)OR₁₉₂, SC(═O)_(i)R₁₉₂, S(═O)_(l)NR₁₉₂R₁₉₂, NR₁₉₂R₁₉₂, NR₁₉₂SO₂R₁₉₂, NR₁₉₂SO₂R₁₉₂R₁₉₂, NR₁₉₂C(═O)R₁₉₂, C(═O)NR₁₉₂R₁₉₂, NR₁₉₂R₁₉₂, oxo or oxime;

[0429] R₁₉₂ is H, C₁₋₄ alkyl, or phenyl;

[0430] at each occurrence, phenyl in R₁₉₁ and R₁₉₂ is optionally substituted with one or more halo, CN, NO₂, phenyl, C₃₋₆ cycloalkyl, OR₁₉₂, C(═O)R₁₉₂, OC(═O)R₁₉₂, C(═O)OR₁₉₂, S(═O)R₁₉₆, S(═O)_(i)NR₁₉₂R₁₉₂, NR₁₉₂SO₂R₁₉₂, NR₁₉₂SO₂NR₁₉₂R₁₉₂, NR₁₉₂C(═O)R₁₉₂, C(═O)NR₁₉₂R₁₉₂, or NR₁₉₂R₁₉₂;

[0431] R₁₉₃ is selected from the group consisting of null, H, C₁-C₄alkyl, C₃-C₅cycloalkyl, C₁-C₄haloalkyl, and halophenyl;

[0432] R₁₉₄ is selected from the group consisting of H, alkyl, C₁-C₂alkoxy, halo, and haloalkoxy, or R₁₉₃ and R₁₉₄ can be taken together to form a 5- or 6-membered, optionally substituted, heteroalkyl or heteroaryl ring;

[0433] R₁₉₅ is H or F;

[0434] R₁₉₆ is selected from the group consisting of H, methyl, amino, and F;

[0435] R₁₉₇ is H, CH₃, or F;

[0436] B is an unsaturated 4-atom linker having one nitrogen and three carbons;

[0437] M is

[0438] a) H,

[0439] b) C₁₋₈ alkyl,

[0440] c) C₃₋₈ cycloalkyl,

[0441] d) —(CH₂)_(m)OR₁₃, or

[0442] e) —(CH₂)_(h)—NR₂₁R₂₂;

[0443] Z is

[0444] a) O,

[0445] b) S, or

[0446] c) NM;

[0447] W is

[0448] a) CH,

[0449] b) N, or

[0450] c) S or O when Z is NM;

[0451] Y is

[0452] a) H,

[0453] b) F,

[0454] c) Cl,

[0455] d) Br,

[0456] e) C₁₋₃ alkyl, or

[0457] f) NO₂;

[0458] X is

[0459] a) H,

[0460] b) —CN,

[0461] c) OR₂₇,

[0462] d) halo,

[0463] e) NO₂,

[0464] f) tetrazoyl,

[0465] g) —SH,

[0466] h) —S(═O)_(i)R₄,

[0467] i) —S(═O)₂—N═S(O)_(j)R₅R₆,

[0468] j) —SC(═O)R₇,

[0469] k) —C(═O)R₂₅,

[0470] l) —C(═O)NR₂₇R₂₈,

[0471] m) —C(═NR₂₉)R₂₅,

[0472] n) —C(R₂₅)(R₂₈)—OR₁₃,

[0473] o) —C(R₂₅)(R₂₈)—OC(═O)R₁₃,

[0474] p) —C(R₂₈)(OR₁₃)—(CH₂)_(h)—NR₂₇R₂₈,

[0475] q) —NR₂₇R₂₈,

[0476] r) —N(R₂₇)C(═O)R₇,

[0477] s) —N(R₂₇)—S(═O)_(i)R₇,

[0478] t) —C(OR₁₄)(OR₁₅)R₂₈,

[0479] u) —C(R₂₅)(R₁₆)—NR₂₇R₂₆, or

[0480] v) C₁₋₈ alkyl substituted with one or more halos, OH, ═O other than at alpha position, —S(═O)_(i)R₁₇, —NR₂₇R₂₈, C₂₋₅ alkenyl, C₂₋₅ alkynyl, or C₃₋₈ cycloalkyl;

[0481] X¹ is N or CR₁₅₈;

[0482] Y₁ is

[0483] a) S(O)_(i),

[0484] b) S(NR₁₅₉), or

[0485] c) S(NR₁₅₉)(O);

[0486] W₁ is O or S;

[0487] X₂ is O or NR₁₆₂;

[0488] X₃ is S(O)_(l) or NR₁₆₆;

[0489] Y₂ is

[0490] a) O

[0491] b) NH,

[0492] c) CH₂, or

[0493] d) S(O)_(i);

[0494] X₄ is

[0495] a) O

[0496] b) NR₁₇₂,

[0497] c) S(O)_(i), or

[0498] d) S(O)(NR₁₇₃); and

[0499] Y₃ is CH or N;

[0500] R₄, R₅, R₆, R₇, R₁₃, R₁₄, R₁₅, R₁₆, and R₁₇ are the same as defined above;

[0501] R₂₅ is

[0502] a) H,

[0503] b) C₁₋₈ alkyl optionally substituted with one or more halos, C₃₋₈ cycloalkyl, C₁₋₄ alkyl substituted with one or more of —S(═O)_(i)R₁₇, —OR₁₃, or OC(═O)R₁₃, NR₂₇R₂₈, or

[0504] c) C₂₋₅ alkenyl optionally substituted with CHO, or CO₂R₁₃;

[0505] R₂₆ is

[0506] a) R₂₈, or

[0507] b) NR₂₇NR₂₈;

[0508] R₂₇ and R₂₈ at each occurrence are the same or different and are

[0509] a) H,

[0510] b) C₁₋₈ alkyl,

[0511] c) C₃₋₈ cycloalkyl,

[0512] d) —(CH₂)_(m)OR₁₃,

[0513] e) —(CH₂)_(h)—NR₂₁R₂₂, or

[0514] f) R₂₇ and R₂₈ taken together are —(CH₂)₂O(CH₂)₂—, (CH₂)_(h)CH(COR₇)—, or —(CH₂)₂N(CH₂)₂(R₇);

[0515] R₂₉ is

[0516] a) —NR₂₇R₂₈,

[0517] b) —OR₂₇, or

[0518] c) —NHC(═O)R₂₈;

[0519] wherein R₃₀ is

[0520] a) H,

[0521] b) C₁₋₈ alkyl optionally substituted with one or more halos, or

[0522] c) C₁₋₈ alkyl optionally substituted with one or more OH, or C₁₋₆ alkoxy;

[0523] wherein E is

[0524] a) NR₃₉,

[0525] b) —S(═O)_(i);

[0526] c) O, or

[0527] d) S(O)(NR₁₉₀);

[0528] R₃₈ is

[0529] a) H,

[0530] b) C₁₋₆ alkyl,

[0531] c) —(CH₂)_(q)-aryl, or

[0532] d) halo;

[0533] R₃₉ is

[0534] a) H,

[0535] b) C₁₋₆ alkyl optionally substituted with one or more OH, halo, or —CN,

[0536] c) —(CH₂)_(q)-aryl,

[0537] d) —CO₂R₄₀,

[0538] e) —COR₄₁,

[0539] f) —C(═O)—(CH₂)_(q)—C(═O)R₄₀,

[0540] g) —S(═O)₂—C₁₋₁₆ alkyl,

[0541] h) —S(═O)₂—(CH₂)_(q)-aryl, or

[0542] i) —(C═O)_(j)-Het;

[0543] R₄₀ is

[0544] a) H,

[0545] b) C₁₋₆ alkyl optionally substituted with one or more OH, halo, or —CN,

[0546] c) —(CH₂)_(q)-aryl, or

[0547] d) —(CH₂)_(q)—OR₄₂;

[0548] R₄₁ is

[0549] a) C₁₋₆ alkyl optionally substituted with one or more OH, halo, or —CN,

[0550] b) —(CH₂)_(q)-aryl, or

[0551] c) —(CH₂)_(q)—OR₄₂;

[0552] R₄₂ is

[0553] a) H,

[0554] b) C₁₋₆ alkyl,

[0555] c) —(CH₂)_(q)-aryl, or

[0556] d) —C(═O)—C₁₋₆ alkyl; aryl is

[0557] a) phenyl,

[0558] b) pyridyl, or

[0559] c) napthyl; a to c optionally substituted with one or more halo, —CN, OH, SH, C₁₋₆ alkyl, C₁₋₆ alkoxy, or C₁₋₆ alkylthio;

[0560] h is 1, 2, or 3;

[0561] i is 0, 1, or 2;

[0562] j is 0 or 1, with the proviso that when j is 0, Y₂ is —CH₂—;

[0563] k is 3, 4, or 5;

[0564] l is 2 or 3;

[0565] m is 4 or 5;

[0566] n is 0, 1, 2, 3, 4, or 5;

[0567] p is 0, 1, 2, 3, 4, or 5; with the proviso that n and p together are 1, 2, 3, 4, or 5;

[0568] q is 1, 2, 3, or 4;

[0569] u is 1 or 2;

[0570] w is 0, 1, 2, or 3;

[0571] x is 0, 1, 2, 3 or 4; and

[0572] y is 0, 1, 2, 3 or 4; with the proviso that x and y taken together are 3 or 4;

[0573] z is 1, 2, 3, 4 or 5, provided that i and z taken together are 2, 3, 4 or 5; and

[0574] G is

[0575] The present invention also provides an oxazolidinone derivative of Formula (II)

[0576] wherein J, R₁, G and A are as defined above.

[0577] The present invention also is directed to an oxazolidinone derivative of formula (VIII) having an improved solubility, wherein R is —CH₂-G-A and R₁, G and A are as defined above.

[0578] The present invention also is directed to a method of improving the solubility of an amide of Formula (III)

[0579] in which the compound of Formula (VIII) is prepared, wherein R is —CH₂-G-A and R₁, G and A are as defined above.

[0580] The present invention also is directed to a method of improving the solubility of an amide of Formula (III)

[0581] in which the compound of Formula (XII) is prepared, wherein R is —CH₂-G-A, with G, A, Q; R₃₁₀, R₄₁₀, R₅₁₀ and R₆₁₀ being as defined above.

[0582] The present invention is also directed to an oxazolidinone derivative of formula (XIII)

[0583] wherein R is -G-A;

[0584] J, G and A being as defined above;

[0585] R₁′ is

[0586] a) H,

[0587] b) OH,

[0588] c) alkyl,

[0589] d) alkoxy,

[0590] e) alkenyl,

[0591] f) amino,

[0592] g) substituted alkyl,

[0593] h) substituted alkoxy,

[0594] i) substituted alkenyl, or

[0595] j) substituted amino,

[0596] R₂₁₀ is

[0597] R₃₁₀, R₄₁₀ and R₅₁₀ each independently are

[0598] a) H,

[0599] b) C₁₋₄ alkyl,

[0600] c) halogen,

[0601] d) C₁₋₄ alkoxy,

[0602] e) hydroxy,

[0603] f) (CH₂)_(c)OP(O)(OH)₂,

[0604] g) C₁₋₄ acyloxy, or

[0605] h) C₁₋₄ alkyl substituted by halogen, hydroxy, acyloxy, NR₁₂₁₀R₁₃₁₀, or alkoxy; and

[0606] R₆₁₀ is

[0607] a) H,

[0608] b) CH₃, or

[0609] c) C₂H₅.

[0610] The present invention is also directed to a method of preparing an oxazolidinone derivative having an improved water solubility comprising the steps of providing an amide of formula (XVI)

[0611] reacting the amide with a compound of formula (XIV)

[0612] to form a compound of formula (XVII)

[0613] and removing the protecting groups to form a compound of formula (XVIII)

[0614] wherein R is -G-A and J, R′₁, G, A and Pr are as described above.

DETAILED DESCRIPTION OF THE INVENTION

[0615] For the purpose of the present invention, the carbon content of various hydrocarbon containing moieties is indicated by a prefix designating the minimum and maximum number of carbon atoms in the moiety, i.e., the prefix C_(l-j) defines the number of carbon atoms present from the integer “i” to the integer “j”, inclusive. Thus, C₁₋₄ alkyl refers to alkyl of 1-4 carbon atoms, inclusive, or methyl, ethyl, propyl, butyl and isomeric forms thereof.

[0616] The terms “C₁₋₂ alkyl”, “C₁₋₃ alkyl”, “C₁₋₄ alkyl”, “C₁₋₅ alkyl”, “C₁₋₆ alkyl”, “C₁₋₈ alkyl”, and “C₁₋₁₆ alkyl” refer to an alkyl group having one to two, one to three, one to four, one to five, one to six, one to eight, or one to sixteen carbon atoms respectively such as, for example, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl and their isomeric forms thereof.

[0617] The terms “C₂₋₄ alkenyl”, “C₂₋₅ alkenyl”, “C₂₋₈ alkenyl”, “C₂₋₁₄ alkenyl” and “C₂₋₁₆ alkenyl” refer to at least one double bond alkenyl group having two to four, two to five, two to eight, two to fourteen, or two to sixteen carbon atoms, respectively such as, for example, ethenyl, propenyl, butenyl, pentenyl, pentdienyl, hexenyl, hexdienyl, heptenyl, heptdienyl, octenyl, octdienyl, octatrienyl, nonenyl, nonedienyl, nonatrienyl, undecenyl, undecdienyl, dodecenyl, tridecenyl, tetradecenyl and their isomeric forms thereof.

[0618] The terms “C₂₋₅ alkynyl”, “C₂₋₈ alkynyl”, and “C₂₋₁₀ alkynyl” refer to at least one triple bond alkynyl group having two to five, two to eight, or two to ten carbon atoms respectively such as, for example, ethynyl, propynyl, butynyl, pentynyl, pentdiynyl, hexynyl, hexdiynyl, heptynyl, heptdiynyl, octynyl, octdiynyl, octatriynyl, nonynyl, nonediynyl, nonatriynyl and their isomeric forms thereof.

[0619] The terms “C₃₋₄ cycloalkyl”, “C₃₋₆ cycloalkyl”, “C₅₋₆ cycloalkyl”, and “C₃₋₈ cycloalkyl” refer to a cycloalkyl having three to four, three to six, five to six, or three to eight carbon atoms respectively such as, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, and their isomeric forms thereof.

[0620] The terms “C₃₋₄ alkoxy”, “C₁₋₆ alkoxy”, and “C₁₋₈ alkoxy” refer to an alkyl group having one to four, one to six, or one to eight carbon atoms respectively attached to an oxygen atom such as, for example, methoxy, ethoxy, propyloxy, butyloxy, pentyloxy, hexyloxy, heptyloxy, or octyloxy and their isomeric forms thereof.

[0621] The terms “C₁₋₆ alkylamino”, and “C₁₋₈ alkylamino” refer to an alkyl group having one to six, or one to eight carbon atoms respectively attached to an amino moiety such as, for example, methylamino, ethylamino, propylamino, butylamino, pentylamino, hexylamino, heptylamino, or octoylamino and their isomeric forms thereof.

[0622] The terms “C₁₋₆ dialkylamino”, and “C₁₋₈ dialkylamino” refer to two alkyl groups having one to six, or one to eight carbon atoms respectively attached to an amino moiety such as, for example, dimethylamino, methylethylamino, diethylamino, dipropylamino, methypropylamino, ethylpropylamino, dibutylamino, dipentylamino, dihexylamino, methylhecylamino, diheptylamino, or dioctoylamino and their isomeric forms thereof.

[0623] The terms “C₁₋₃ acyl”, “C₁₋₄ acyl”, “C₁₋₅ acyl”, “C₁₋₆ acyl”, “C₁₋₈ acyl”, and “C₂₋₈ acyl” refer to a carbonyl group having an alkyl group of one to three, one to four, one to five, one to six, one to eight, or two to eight carbon atoms.

[0624] The terms “C₁₋₄ alkoxycarbonyl”, “C₁₋₆ alkoxycarbonyl”, and “C₁₋₈ alkoxycarbonyl” refer to an ester group having an alkyl group of one to four, one to six, or one to eight carbon atoms.

[0625] The term “C₁₋₈ alkyl phenyl” refers to an alkyl group having one to eight carbon atoms and isomeric forms thereof which is substituted with at least one phenyl radical.

[0626] The term “C₂₋₈ alkenyl phenyl” refers to a at least one double bond alkenyl group having one to eight carbon atoms and isomeric forms thereof which is substituted with at least one phenyl radical.

[0627] The term “C₁₋₈ alkyl pyridyl” refers to an alkyl group having one to eight carbon atoms and isomeric forms thereof which is substituted with at least one pyridyl radical.

[0628] The term “C₁₋₈ hydroxyl” refers to an alkyl group having one to eight carbon atoms and isomeric forms thereof attached to a hydroxy group.

[0629] The term “C₁₋₈ alkylsulfonyl” refers to an alkyl group having one to eight carbon atoms and isomeric forms thereof attached to a SO₂ moiety.

[0630] The term “C₁₋₆ alkylthio” refers to an alkyl group having one to six carbon atoms and isomeric forms thereof attached to a sulfur atom.

[0631] The term “Het” refers to 5 to 10 membered saturated, unsaturated or aromatic heterocyclic rings containing one or more oxygen, nitrogen, and sulfur forming such groups as, for example, pyridine, thiophene, furan, pyrazoline, pyrimidine, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, 3-pyrazinyl, 2-quinolyl, 3-quinolyl, 1-isoquinolyl, 3-isoquinolyl, 4-isoquinolyl, 2-quinazolinyl, 4-quinazolinyl, 2-quinoxalinyl, 1-phthalazinyl, 4-oxo-2-imidazolyl, 2-imidazolyl, 4-imidazolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 3-pyrazolyl, 4-pyrazolyl, 5-pyrazolyl, 2-oxazolyl, 4-oxazolyl, 4-oxo-2-oxazolyl, 5-oxazolyl, 4,5,-dihydrooxazole, 1,2,3-oxathiole, 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,2,5-oxadiazole, 1,3,4-oxadiazole, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 3-isothiazole, 4-isothiazole, 5-isothiazole, 2-indolyl, 3-indolyl, 3-indazolyl, 2-benzoxazolyl, 2-benzothiazolyl, 2-benzimidazolyl, 2-benzofuranyl, 3-benzofuranyl, benzoisothiazole, benzisoxazole, 2-furanyl, 3-furanyl, 2-thienyl, 3-thienyl, 2-pyrrolyl, 3-pyrrolyl, 3-isopyrrolyl, 4-isopyrrolyl, 5-isopyrrolyl, 1,2,3,-oxathiazole-1-oxide, 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl, 5-oxo-1,2,4-oxadiazol-3-yl, 1,2,4-thiadiazol-3-yl, 1,2,4-thiadiazol-5-yl, 3-oxo-1,2,4-thiadiazol-5-yl, 1,3,4-thiadiazol-5-yl, 2-oxo-1,3,4-thiadiazol-5-yl, 1,2,4-triazol-3-yl, 1,2,4-triazol-5-yl, 1,2,3,4-tetrazol-5-yl, 5-oxazolyl, 1-pyrrolyl, 1-pyrazolyl, 1,2,3-triazol-1-yl, 1,2,4-triazol-1-yl, 1-tetrazolyl, 1-indolyl, 1-indazolyl, 2-isoindolyl, 7-oxo-2-isoindolyl, 1-purinyl, 3-isothiazolyl, 4-isothiazolyl and 5-isothiazolyl, 1,3,4,-oxadiazole, 4-oxo-2-thiazolinyl, or 5-methyl-1,3,4-thiadiazol-2-yl, thiazoledione, 1,2,3,4-thiatriazole, 1,2,4-dithiazolone. Each of these moieties may be substituted as appropriate.

[0632] The term het¹ at each occurrence is independently a C-linked 5- or 6-membered heterocyclic ring having 1 to 4 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur within the ring.

[0633] The term het² at each occurrence is independently a N-linked 5- or 6-membered heterocyclic ring having 1 to 4 nitrogen and optionally having one oxygen or sulfur within the ring.

[0634] The term Het₁ is a 5- or 6-membered heteroaromatic moiety having 1-3 N, O or S atoms, optionally substituted with the following:

[0635] a) F,

[0636] b) Cl,

[0637] c) C₁₋₃ alkoxy,

[0638] d) C₁₋₃ alkylthio, or

[0639] e) CN.

[0640] The term het₁ is a C-linked 5- or 6-membered saturated or unsaturated heterocyclic ring having 1, 2, or 3 heteroatoms selected from the group consisting of oxygen, sulfur, and nitrogen, which is optionally fused to a benzene ring.

[0641] The term halo refers to fluoro, chloro, bromo, or iodo.

[0642] The term Pr refers to a suitable phosphate protecting group, such as benzyl, alkyl, tert-butyl, etc.

[0643] The compounds of the present invention can be converted to their salts, where appropriate, according to conventional methods.

[0644] The term “pharmaceutically acceptable salts” refers to acid addition salts useful for administering the compounds of this invention and include hydrochloride, hydrobromide, hydroiodide, sulfate, phosphate, acetate, propionate, lactate, mesylate, maleate, malate, succinate, tartrate, citric acid, 2-hydroxyethyl sulfonate, fumarate and the like. These salts may be in hydrated form.

[0645] When Q is the structure of

[0646] the dotted line in the heterocyclic ring means that this bond can be either single or double. In the case where the dotted line is a double bond, the R₃₉ group will not be present.

[0647] The compounds of this invention contain a chiral center at CS of the isoxazoline ring, and as such there exist two enantiomers or a racemic mixture of both. This invention relates to both the enantiomers, as well as mixtures containing both the isomers. In addition, depending on substituents, additional chiral centers and other isomeric forms may be present in any of A or R₁ group, and this invention embraces all possible stereoisomers and geometric forms in these groups.

[0648] The compounds of this invention are useful for treatment of microbial infections in humans and other warm blooded animals, under both parenteral and oral administration. The inventive compounds have antibacterial activity against a number of human and veterinary pathogens including Gram-positive aerobic bacteria such as multiply-resistant staphylococci, streptococci and enterococci, Gram-negative organisms such as H. influenzae and M. catarrhalis, anaerobic organisms such as Bacteroides spp. and Clostridasppa, Mycobacterium tuberculosis, M. avium and M. spp. and organisms such as Mycoplasma spp.

[0649] The pharmaceutical compositions of this invention may be prepared by combining the compounds of this invention with a solid or liquid pharmaceutically acceptable carrier and, optionally, with pharmaceutically acceptable adjuvants and excipients employing standard and conventional techniques. Solid form compositions include powders, tablets, dispersible granules, capsules, cachets and suppositories. A solid carrier can be at least one substance which may also function as a diluent, flavoring agent, solubilizer, lubricant, suspending agent, binder, tablet disintegrating agent, and encapsulating agent. Inert solid carriers include magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, starch, gelatin, cellulosic materials, low melting wax, cocoa butter, and the like. Liquid form compositions include solutions, suspensions and emulsions. For example, there may be provided solutions of the compounds of this invention dissolved in water and water-propylene glycol and water-polyethylene glycol systems, optionally containing suitable conventional coloring agents, flavoring agents, stabilizers and thickening agents.

[0650] Preferably, the pharmaceutical composition is provided employing conventional techniques in unit dosage form containing effective or appropriate amounts of the active component, that is, the compound according to this invention.

[0651] The quantity of active component, that is the compound according to this invention, in the pharmaceutical composition and unit dosage form thereof may be varied or adjusted widely depending upon the particular application, the potency of the particular compound, the desired concentration. Generally, the quantity of active component will range between 0.5% to 90% by weight of the composition.

[0652] In therapeutic use for treating, or combatting, bacterial infections in warm-blooded animals, the compounds or pharmaceutical compositions thereof will be administered orally, parenterally and/or topically at a dosage to obtain and maintain a concentration, that is, an amount, or blood-level of active component in the animal undergoing treatment which will be antibacterially effective. Generally, such antibacterially effective amount of dosage of active component will be in the range of about 0.1 to about 100, more preferably about 3.0 to about 50 mg/kg of body weight/day. It is to be understood that the dosages may vary depending upon the requirements of the patient, the severity of the bacterial infection being treated, and the particular compound being used. Also, it is to be understood that the initial dosage administered may be increased beyond the above upper level in order to rapidly achieve the desired blood-level or the initial dosage may be smaller than the optimum and the daily dosage may be progressively increased during the course of treatment depending on the particular situation. If desired, the daily dose may also be divided into multiple doses for administration, e.g., 2-4 four times per day.

[0653] When the compounds according to this invention are administered parenterally, i.e., by injection, for example, by intravenous injection or by other parenteral routes of administration. Pharmaceutical compositions for parenteral administration will generally contain a pharmaceutically acceptable amount of the compound or a soluble salt (acid addition salt or base salt) dissolved in a pharmaceutically acceptable liquid carrier such as, for example, water-for-injection and a buffer to provide a suitably buffered isotonic solution, for example, having a pH of about 3.5-6. Suitable buffering agents include, for example, trisodium orthophosphate, sodium bicarbonate, sodium citrate, N-methylglucamine, L(+)-lysine and L(+)-arginine to name but a few representative buffering agents. The compound of this invention generally will be dissolved in the carrier in an amount sufficient to provide a pharmaceutically acceptable injectable concentration in the range of about 1 mg/mL to about 400 mg/mL of solution. The resulting liquid pharmaceutical composition will be administered so as to obtain the above-mentioned antibacterially effective amount of dosage. The compounds according to this invention are advantageously administered orally in solid and liquid dosage forms.

[0654] As a topical treatment an effective amount of Formula I is admixed in a pharmaceutically acceptable gel or cream vehicle that can be applied to the patient's skin at the area of treatment. Preparation of such creams and gels is well known in the art and can include penetration enhancers.

[0655] The present invention improves the solubility and bioavailability of an amide of Formula III

[0656] by converting it into a prodrug of Formula (VIII). The general scheme for preparing the prodrug of Formula (VIII) is shown below in Schemes 1 and 2.

[0657] In the above reaction scheme, the carboxylic acid derivative of Formula IV is prepared as described in M. G. Nicolaou, C. -S. Yuan and R. T. Borchardt, J. Med. Chem. 1996, 61, 8636-8641. Condensation of the amine of Formula V with the carboxylic acid of IV is accomplished by methods known in the art for amide or peptide bond formation. Examples include 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 4-(dimethylamino)pyridine and solvents such as methylene chloride at reaction temperatures of 0 to 24° C., 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 1-hydroxybenzotriazole and solvents such as dimethylformamide at 0 to 24° C., and bis(2-oxo-3-oxazolidinyl)phosphinic chloride and triethylamine and solvents such as methylene chloride at 0 to 24° C.

[0658] In Step 2 of Scheme 1, the amide of VI undergoes an acylation reaction to give the compound of VII, wherein J is an oxygen atom. This reaction is conveniently carried out by allowing the compound of VI to react with an acid chloride in the presence of an efficient acid scavenger. Solvents such as methylene chloride, ethylene chloride or carbon tetrachloride at a temperature of from 24° C. to the reflux temperature of the solvent can be used. Acid scavengers such as 3 Å units molecular sieves, propylene oxide, 1,8-bis(dimethylamino)naphthalene and methyl trimethylsilylcarbamate are suitable for use in this reaction. In Step 3 of Scheme 1, the phosphate esters of Formula VII are deprotected. This can be carried out by hydrogenolysis at atmospheric pressure and ambient temperature with a palladium catalyst. Solvents such as tetrahydrofuran, diethylether, or 1,2-dimethoxyethane can be used for this reaction.

[0659] Alternatively, compounds of formula (VIII) can be prepared according to the following Scheme 2. In Scheme 2, P_(r) of formula (XIII) represents a suitable phosphate protecting group, such as benzyl, alkyl or tert-butyl.

[0660] In Step 1, the acid (XIII) is converted to the acid chloride (XIV) with, for example, oxalyl chloride and dimethylformamide in a solvent, such as methylene chloride, at temperatures of from 0 to 30° C. In Step 2, the compound of formula (XIV) is allowed to react with the compound of formula (III) in a solvent, such as methylene chloride, ethylene chloride or acetonitrile, in the presence of an efficient acid scavenger, such as methyl trimethylsilylcarbamate, at the reflux temperature of the solvent. In Step 3, the phosphate protecting groups of the compound of formula (XV) is removed by methods known in the art.

[0661] Examples of amides containing oxazolidinone groups that can be used in the present invention are shown below. The preparation of the following amides of Examples 1-434 are shown in U.S. Pat. No. 6,362,189 B1, the disclosure of which is herein incorporated by reference thereto. TABLE A EXAMPLE 1: (S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]- 2-oxo-5-oxazolidinyl]methyl]thioacetamide (I) EXAMPLE 2: (S)-N-[[3-[3-Fluoro-4-[4-(5-methyl-1,3,4- thiadiazol-2-yl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]thioacetamide (2) EXAMPLE 3: (S)-N-[[3-[3-Fluoro-4-[2′,5′- dioxospiro[piperidine-4,4′-imidazolidine]-1-yl]phenyl]- 2-oxo-5-oxazolidinyl]methyl]thioacetamide (3). EXAMPLE 4: (S)-N-[[3-[3-Fluoro-4-(4- morpholinyl)phenyl]-2-oxo-5- oxazolidinyl]methyl]thioacetamide (4). EXAMPLE 5: (S)-cis-N-[[3-[3-Fluoro-4-(tetrahydro-1- oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]ethanethioamide EXAMPLE 6: (S)-trans-N-[[3-[3-Fluoro-4-(tetrahydro-1- oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]ethanethioamide EXAMPLE 7: (S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,1- dioxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5- oxazolidinyl]methyl]ethanethioamide EXAMPLE 8: (S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]- 2-oxo-5-oxazolidinyl]methyl]-thioformamide (7). EXAMPLE 9: (S)-N-[[3-[3-Fluoro-4-(4-morpholinyl)phenyl]- 2-oxo-5-oxazolidinyl]methyl]thiopropion-amide (9). EXAMPLE 10: (S)-N-[[3-[3-Fluoro-4-(4- morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2- chlorothioacetamide (11). EXAMPLE 11: (S)-N-[[3-[3-Fluoro-4-(4- moropholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-α,α, α-trifluorothioacetamide (13). EXAMPLE 12: (S)-N-[[3-[3-Fluoro-4-(4- morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-α- fluorothioacetamide (15). EXAMPLE 13: (S)-N-[[3-[3-Fluoro-4-(4- morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-α,α- difluorothioacetamide (17). EXAMPLE 14: (S)-N-[[3-[3-Fluoro-4-(4- morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-α- cyanothioacetamide (19). EXAMPLE 15: (S)-N-[[3-[3-Fluoro-4-(4- morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-α,α- dichlorothioacetamide (21). EXAMPLE 16: (S)-N-[[3-[3-Fluoro-4-(4- morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-α- (methoxycarbonyl)thioacetamide (23). EXAMPLE 17: (S)-N-[[3-[4-[1-[1,2,4]Triazolyl]phenyl]-2- oxo-5-oxazolidinyl]methyl]thioacetamide (25). EXAMPLE 18: (S)-N-[[3-[4-[1-[1,2,4]Triazolyl]phenyl]-2- oxo-5-oxazolidinyl]methyl]thioacetamide (25). EXAMPLE 19: (S)-N-[[3-[1-(Hydroxyacetyl)-5-indolinyl]-2- oxo-5-oxazolidinyl]methyl]thioacetamide (28). EXAMPLE 20: (S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1- piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]thioacetamide (30). EXAMPLE 21: (S)-N-[[3-[3-Fluoro-4-(4- thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thio- acetamide (32). EXAMPLE 22: (S)-N-[[3-[3-Fluoro-4-(4- thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thio- acetamide, thiomorpholine S-oxide (34). EXAMPLE 23: (S)-N-[[3-[3-Fluoro-4-(4- thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thio- acetamide, thiomorpholine S, S-dioxide (36). EXAMPLE 24: (S)-N-[[3-[3,5-Difluoro-4-[4- (hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]thioacetamide (38).

[0662] TABLE B

Example No. Compound R, R′ 25 (S)-N-[[3-[3-Fluoro-4-(4-morp R = H, R′ = holinyl)- CH(CH₃)₂ phenyl]-2-oxo-5-oxazolidinyl] methyl]-2- methylpropanethioamide; mp 152-153°C. (dec.); Anal. calcd for C₁₈H₂₄FN₃O₃S: C, 56.67; H, 6.34; N, 11.02. Found: C, 56.58; H, 6.41; N, 10.81 26 (S)-N-[[3-[3-Fluoro-4-(4-morp holinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropane-carbothioamide; mp 155-156° C.; Anal. calcd for C₁₈H₂₂FN₃O₃S: C, 56.98; H, 5.84; N, 11.07. Found: C, 56.98; H, 5.85; N, 10.97 27 (S)-N-[[3-[3,5-Difluoro-4-(4- R = F, R′ = CH₃ morpholinyl)- phenyl]-2-oxo-5-oxazolidinyl] methyl]thioacetamide

[0663] TABLE C Dithio Compound Example (from No. Compound Amine Prepartion Z) 28 (S)-N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide, thiomorphoilne S-oxide; mp 196-197° C.; Anal. calcd for C₁₇H₂₂FN₃O₃S₂: C, 51.11; H, 5.55; # N, 10.52; S, 16.05. Found: C, 50.99; H, 5.60 N, 10.55; S, 15.75

Z (a) 29 S)-N-[[3-[3-Fluoro-4-(4- Same as Z (b) thiomorpholinyl)- above phenyl]-2-oxo-5 oxazolidinyl]methyl]-2- methylpropanethioamide, thiomorpholine S-oxide; mp 195-196° C.; Anal. calcd for C₁₈H₂₄FN₃O₃S₂: C, 52.28; H, 5.85; N, 10.16; S, 15.51. Found: C, 52.24; H, 5.97; N, 10.16; S, 15.28 30 (S)-N-[[3-[3-Fluoro-4- Same as Z (c) (4-thiomorpholinyl)- above phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothioamide, thiomorpholine S-oxide; mp 109-110° C.; Anal. calcd for C₁₈H₂₂FN₃O₃S₂: C, 52.54; H, 5.39; N, 10.21; S, 15.58. Found: C, 52.48; H, 5.51; N, 10.28; S, 15.29 31 (S)-N-[[3-[3-Fluoro-4- Same as Z (d) (4-thiomorpholiny above 1)phenyl]-2-oxo-5 oxazolidinyl]methyl] butanethioamide, thiomorpholine S-oxide 32 (S)-N-[[3-[3-Fluoro-4- Same as Z (e) (4-thiomorpholinyl) above phenyl]-2-oxo-5 oxazolidinyl]methyl]-3 methylbutanethioamide, thiomorpholine S-oxide 33 (S)-N-[[3-[3-Fluoro-4- Same as Z (f) (4-thiomorpholinyl) above phenyl]-2-oxo-5 oxazolidinyl]methyl]-2 methylbutanethioamide, thiomorpholine S-oxide 34 (S)-N-[[3-[3-Fluoro-4- Same as Z (g) (4-thiomorpholinyl) above phenyl]-2-oxo-5 oxazolidinyl]methyl] 3,3-dimethylbutanethioamide, thiomorpholine S-oxide 35 (S)-N-[[3-[3-Fluoro-4- Same as Z (h) (4-thiomorpholinyl) above phenyl]-2-oxo-5 oxazolidinyl]methyl] cyclobutanecarbothioamide, thiomorpholine S-oxide 36 (S)-N-[[3-[3-Fluoro-4- Same as Z (i) (4-thiomorpholinyl) above phenyl]-2-oxo-5 oxazolidinyl]methyl]-1- cyclopentanecarbothioamide, thiomorpholine S-oxide 37 (S)-N-[[3-[3-Fluoro-4- Same as above Z(j) (4-thiomorpholinyl) phenyl]-2-oxo-5 oxazolidinyl]methyl] cyclohexanecarbothioamide, thiomorpholine S-oxide 38 (S)-N-[(3-[3-Fluoro-4- Same as above Z (k) (4-thiomorpholinyl)- phenyl]-2-oxo-5 oxazolidinyl]methyl]-2- cyclopropylethanethioamide, thiomorpholine S-oxide 39 (S)-N-[[3-[3-Fluoro-4- Same as above Z (l) (4-thiomorpholinyl)- phenyl]-2-oxo-5 oxazolidinyl]methyl]-2- cyclobutylethanethioamide, thiomorpholine S-oxide 40 (S)-N-[[3-[3-Fluoro-4- Same as above Z (m) (4-thiomorpholinyl)- phenyl]-2-oxo-5 oxazolidinyl]methyl]-2- cyclopentylethanethioamide, thiomorpholine S-oxide 41 (S)-N-[[3-[3-Fluoro-4- (4-thiomorpholinyl)- phenyl]-2-oxo-5 oxazolidinyl]methyl]- thioacetamide, thiomorpholine S-oxide

Ethyl dithioacetate 42 (S)-N-[[3-[3-Fluoro-4- Same as above Z (a) (4-thiomorpholinyl)- phenyl]-2-oxo-5 oxazolidinyl]methyl]- propanethioamide, thiomorpholine S-oxide 43 (S)-N-[[3-[3-Difluoro- Same as Z (b) 4- above (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide, thiomorpholine S-oxide 44 (S)-N-[[3-[3-Difluoro- Same as Z (c) 4- above (4-thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothioamide, thiomorpholine S-oxide 45 (S)-N-[[3-[4-(4 thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidiny]methyl]- thioacetamide, thiomorpholine S-oxide

Ethyl dithioacetate 46 (S)-N-[[3-[4-(4 Same as Z (a) thiomorpholinyl)- above phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide, thiomorpholine S-oxide 47 (S)-N-[[3-[4-(4 Same as Z (b) thiomorpholinyl)- above phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide, thiomorpholine S-oxide 48 (S)-N-[[3-[4-(4 Same as Z (c) thiomorpholinyl)- above phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothioamide, thiomorpholine S-oxide 49 (S)-N-[[3-[3,5- Difluoro-4-(4- hydroxyacetyl)-1- piperazinyl]pheny 1]-2-oxo-5- oxazolidinyl]- methyl]propanethioamide

Z (a) 50 (S)-N-[[3-[3,5- Same as Z (b) Difluoro-4-(4- above hydroxyacetyl)-1- piperazinyl]pheny-1]-2- oxo-5- oxazolidinyl]- methyl]-2-methyl- propanethioamide 51 (S)-N-[[3-[3,5- Same as Z (c) Difluoro-4-(4- above hydroxyacetyl)-1- piperazinyl]pheny-1]-2- oxo-5- oxazolidinyl]- methyl]cyclopropanethioamide 52 (S)-N-[[3-[3-[4 (hydroxyacetyl)-1- piperazinyl]pheny 1]-2-oxo-5- oxazolidinyl]- methyl]propanethioamide

Z (a) 53 (S)-N-[[3-[3-[4 Same as Z (b) (hydroxyacetyl)- above 1- piperazinyl]pheny 1]-2- oxo-5- oxazolidinyl]- methyl]-2-methyl- propanethioamide 54 (S)-N-[[3-[3-[4 Same as Z (c) (hydroxyacetyl)- above 1- piperazinyl]pheny 1]-2- oxo-5- oxazolidinyl]- methyl]cyclopropane- carbothioamide

[0664] TABLE D Dithio Compound Example (from No. Compound Amine Preparation Z) 55 (S)-N-[[3-[3- Fluoro-4- (4- thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]meth yl]- propanethioamide, thiomorpholine 5,5- dioxide

Z (a) 56 (S)-N-[[3-[3- Same as Z (b) Fluoro-4- above (4- thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]meth yl]-2- methylpropanethio amide, thiomorpholine S,S-dioxide 57 (S)-N-[[3-[3- Same as Z (c) Fluoro-4- above (4- thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]meth yl]- cyclopropanecarbo thio- amide, thiomorpholine S,S-dioxide 58 (S)-N-[[3-[3,5- Difluoro- 4-(4- thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]- methyl]thioacetam ide, thiomorpholine S,S- dioxide

59 (S)-N-[[3-[3,5- Same as Z (a) Difluoro- above 4-(4- thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]meth yl]- propanethioamide, thiomorpholine S,S- dioxide 60 (S)-N-[[3-[3,5- Same as Z (b) Difluoro- above 4-(4- thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]meth yl]-2- methylpropanethio — amide, thiomorpholine S,S-dioxide 61 (S)-N-[[3-[3,5- Same as Z (c) Difluoro- above 4-(4- thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]meth yl] cyclopropanecarbo thio- amide, thiomorpholine S,S-dioxide 62 (S)-N-[[3-[4-(4- thio- morpholinyl)pheny 1]-2-oxo-5- oxazolidinyl]- methyl]thioacetam ide, thiomorpholine S,S-dioxide

Ethyl dithioacetate 63 (S)-N-[[3-[4-(4- Same as Z (a) thio- above morpholinyl)pheny 1]-2-oxo-5- oxazolidinyl]- methyl]propanethi o- amide, thiomorpholine S,S-dioxide 64 (S)-N-[[3-[4-(4- Same as Z (b) thio- above morpholinyl)pheny 1]-2-oxo-5- oxazolidinyl]- methyl]-2-methyl- propanethioamide, thiomorpholine S,S-dioxide 65 (S)-N-[[3-[4-(4- Same as Z (c) thio- above morpholinyl)pheny 1]-2-oxo-5- oxazolidinyl]- methyl]cyclopropa ne- carbothioamide, thiomorpholine S,S-dioxide

[0665] TABLE E Dithio Compound Example (from No. Compound Amine Preparation Z) 66 (S)-N[[3-[3- Fluoro-4- (4- thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]meth yl]- propanethioamide

Z (a) 67 (S)-N-[[3-[3- Same as Z (b) Fluoro-4- above (4- thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]meth yl]-2- methylpropanethio amide 68 (S)-N-[[3-[3- Same as Z (c) Fluoro-4- above (4- thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]meth yl]- cyclopropanecarbo thio- amide 69 (S)-N-[[3-[3- Same as Z (d) Fluoro-4- above (4- thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]meth yl] butanethioamide 70 (S)-N-[[3-[3- Same as Z (e) Fluoro-4- above (4- thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]meth yl]-3- methylbutanethioa mide 71 (S)-N-[[3-[3- Same as Z (f) Fluoro-4- above (4- thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]meth yl]-2- methylbutanethioa mide 72 (S)-N-[[3-[3- Same as Z (g) Fluoro-4- above (4- thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]meth yl]- 3,3- dimenthylbutaneth io- amide 73 (S)-N-[[3-[3- Same as Z (h) Fluoro-4- above (4- thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]meth yl]- cyclobutanecarbot hio- amide 74 (S)-N-[[3-[3- Same as Z (i) Fluoro-4- above (4- thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]meth yl]- cyclopentanecarbo thio- amide 75 (S)-N-[[3-[3- Same as Z (j) Fluoro-4- above (4- thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]meth yl]- cyclohexanecarbot hio amide 76 (S)-N-[[3-[3- Same as Z (k) Fluoro-4- above (4- thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]meth yl]-2- cyclopropylethane thio- amide 77 (S)-N-[[3-[3- Same as Z (l) Fluoro-4- above (4- thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]meth yl]-2- cyclobutylethanet hio- amide 78 (S)-N-[[3-[3- Same as Z (m) Fluoro-4- above (4- thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]meth yl]-2- cyclopentylethane thio- amide 79 (S)-N-[[3-[3,5- Difluoro- thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]meth yl]thioacetamide

Ethyl dithioacetate 80 (S)-N-[[3-[3,5- Same as Z (a) Difluoro- above 4-(4- thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]meth yl] propanethioamide 81 (S)-N-[[3-[3,5- Same as Z (b) Difluoro- above 4-(4- thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]meth yl]-2- methylpropanethio amide 82 (S)-N-[[3-[3,5- Same as Z (c) Difluoro- above 4-(4- thiomorpholinyl)- phenyl]-2-oxo-5- oxazolidinyl]meth yl] cyclopropanecarbo thio-amide 83 (S)-N-[[3-[4-(4- thio- morpholinyl)pheny 1]-2-oxo-5- oxazolidinyl]- methyl]thioacetam ide

84 (S)-N-[[3-[4-(4- Same as Z (a) thio- above morpholinyl)pheny 1]-2-oxo-5- oxazolidinyl]- methyl]propanethi o- amide 85 (S)-N-[[3-[4-(4- Same as Z (b) thio- above morpholinyl)pheny 1]-2-oxo-5- oxazolidinyl]- methyl]-2-methyl- propanethioamide 86 (S)-N-[[3-[4-(4- Same as Z (c) thio- above morpholinyl)pheny 1]-2-oxo-5- oxazolidinyl]- methyl]cyclopropa ne- carbothioamide

EXAMPLE 87

[0666] (S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-1-azetidinecarbothioamide, Thiomorpholine S-oxide; Anal. Calcd for C₁₈H₂₃FN₄O₃S₂, C, 50.69; H, 5.43; N, 13.14. Found: C, 50.79; H, 5.45; N, 12.82; mp 213-214° C.

EXAMPLE 88

[0667] (S)-N-[[3-[3-Fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-1-azetidinecarbothioamide

EXAMPLE 89

[0668] (S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]ph enyl-2-oxo-5-oxazolidinyl]methyl]propanethioamide TABLE F

Example No. Compound 90 (S)-N-[[3-[3-Fluoro-4-[4-(hy R = CH(CH₃)₂ droxy- acetyl)-1-piperazinyl]phenyl ]-2-oxo-5- oxazolidinyl]methyl]-2-methy lpropane-thioamide; Anal. calcd for C₂₀H₂₇FN₄O₄S: C, 54.78; H, 6.21; N, 12.78; S, 7.21. Found: C, 54.67; H, 6.34; N, 12.41; S, 7.15 91 (S)-N-[[3-[3-Fluoro-4-[4-( hydroxy- acetyl)-1-piperazinyl]phen yl]-2-oxo-5- oxazolidinyl]methyl]cyclop ropane-carbothioamide; mp 179-181° C.; Anal. calcd for C₂₀H₂₅FN₄O₄S: C, 55.03; H, 5.77; N, 12.84; 5, 7.34. Found: C, 55.15; H, 5.72; N, 12.76; 5, 7.09

92 (S)-N-[[3-[3-Fluoro-4-[4-( R = CH₂—CH₂—CH₃ hydroxy- acetyl)-1-piperazinyl]phen yl]-2-oxo-5- oxazolidinyl]methyl]butane thioamlde 93 (S)-N-[[3-[3-Fluoro-4-[4-( hydroxy- acetyl)-1-piperazinyl]phen yl]-2-oxo-5- oxazolidinyl]methyl]-3-met hylbutane- thioamide

94 (S)-N-[[3-[3-Fluoro-4-[4-( hydroxy- acetyl)-1-piperazinyl]phen yl]-2-oxo-5- oxazolidinyl]methyl]-2-met hylbutane thioamide

95 (S)-N-[[3-[3-Fluoro-4-[4-( R = CH₂—C(CH₃)₃ hydroxy acetyl)-1-piperazinyl]phen yl]-2-oxo-5- oxazolidinyl oxazolidinyl]methyl]-3,3-d imethyl- butanethioamide 96 (S)-N-[[3-[3-Fluoro-4-[4-( hydroxy- acetyl)-1-piperazinyl]phen yl]-2-oxo-5- oxazolidinyl]methyl]cyclob utane-carbothioamide

97 (S)-N-[[3-[3-Fluoro-4-[4-( hydroxy- acetyl)-1-piperazinyl]phen yl]-2-oxo-5- oxazolidinyl]methyl]cyclop entane- carbothioamide

98 (S)-N-[[3-[3-Fluoro-4-[4-( hydroxy- acetyl)-1-piperazinyl]phen yl]-2-oxo-5- oxazolidinyl]methyl]cycloh exane- carbothioamide

99 (S)-N-[[3-[3-Fluoro-4-[4-( hydroxy- acetyl)-1-piperazinyl]phen yl]-2-oxo-5- oxazolidinyl]methyl]-2-cyc lopropyl-ethanethioamide

100  (S)-N-[[3-[3-Fluoro-4-[4-(hy droxy- acetyl)-1-piperazinyl]phenyl ]-2-oxo-5- oxazolidinyl]methyl]-2-cyclo butyl ethanethioamide

101  (S)-N-[[3-[3-Fluoro-4-[4-(hy droxy- acetyl)-1-piperazinyl]phenyl ]-2-oxo-5- oxazolidinyl]methyl]-2-cyclo pentylethanethioamide

EXAMPLE 102

[0669] (S)-N-[[3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]ph enyl]-2oxo-5-oxazolidinyl]methyl]-1-azetidinecarbothioamide.

EXAMPLE 103

[0670] (S)-N-[[3-Fluoro-4-(4-acetyl-1-piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide TABLE G Dithio Example No. Product Amine Compound 104 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1- P-90 Z (a) piperazinyl)phenyl]-2-oxo-5- oxazolidinyl]methyl]propanethioamide; mp 161-162° C.; Anal. calcd for C₁₉H₂₅FN₄O₃S: C, 55.87; H, 6.17; N, 13.72; S, 7.85. Found: C, 55.79; H, 6.26; N, 13.60; S, 7.71 105 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1- P-90 Z (b) piperazinyl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-methylpropane- thioamide 106 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1- P-90 Z (c) piperazinyl)phenyl]-2-oxo-5- oxazolidinyl]methyl]cyclopropanecarbo- thioamide; mp 159-160° C.; Anal. calcd for C₂₀H₂₅FN₄O₃S: C, 57.13; H, 5.99; N, 13.32; S, 7.62. Found: C, 57.05; H, 6.01; N, 13.15; S, 7.45. 107 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1- P-90 Z (d) piperazinyl)phenyl]-2-oxo-5- oxazolidinyl]methyl]butanethioamide 108 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1- P-90 Z (e) piperazinyl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-3-methylbutanethioamide 109 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1- P-90 Z (f) piperazinyl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-methylbutane-thioamide 110 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1- P-90 Z (g) piperazinyl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-3,3-dimethylbutane- thioamide 111 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1- P-90 Z (h) piperazinyl)phenyl]-2-oxo-5- oxazolidinyl]methyl]cyclobutanecarbo-thioamide 112 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1- P-90 Z (i) piperazinyl)phenyl]-2-oxo-5- oxazolidinyl]methyl]cyclopentanecarbo- thioamide 113 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1- P-90 Z (j) piperazinyl)phenyl]-2-oxo-5- oxazolidinyl]methyl]cyclohexanecarbo- thioamide 114 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1- P-90 Z (k) piperazinyl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-cyclopropylethane- thioamide 115 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1- P-90 Z (l) piperazinyl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-cyclobutylethane- thioamide 116 (S)-N-[[3-[3-Fluoro-4-(4-acetyl-1- P-90 Z (m) piperazinyl)phenyl]-2-oxo-5- oxazolidinyl]methyl]-2-cyclopentylethane- thioamide 117 (S)-N-[[3-[3,5-Difluoro-4-(4-acetyl- P-91 Ethyl 1-piperazinyl)- dithio- phenyl]-2-oxo-5-oxazolidinyl]methyl] acetate thioacetamide 118 (S)-N-[[3-[3,5-Difluoro-4-(4-acetyl- P-91 Z (a) 1-piperazinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl] propane-thioamide 119 (S)-N-[[3-[3,5-Difluoro-4-(4-acetyl- P-91 Z (b) 1-piperazinyl)- phenyl]-2-oxo-5-oxazolidinyl] methyl]-2-methyl-propanethioamide 120 (S)-N-[[3-[3, 5-Difluoro-4-(4-acetyl- P-91 Z (c) 1-piperazinyl)- phenyl]-2-oxo-5-oxazolidinyl]methyl] cycloproane- carbothioamide 121 (S)-N-[[3-[4-(4-Acetyl-1- P-92 Ethyl piperazinyl)-2-oxo-5- dithio- oxazolidinyl]methyl]thioacetamide acetate 122 (S)-N-[[3-[4-(4-Acetyl-1- P-92 Z (a) piperazinyl)-2-oxo-5- oxazolidinyl]methyl]propanethioamide 123 (S)-N-[[3-[4-(4-Acetyl-1- P-92 Z (b) piperazinyl)-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide 124 (S)-N-[[3-[4-(4-Acetyl-1- P-92 Z (c) piperazinyl)-2-oxo-5- oxazolidinyl]methyl]cyclopropane- carbothioamide 125 (S)-N-[[3-[3-Fluoro-4-[4- P-93 Ethyl (methoxyacetyl)-1- dithio- piperazinyl]phenyl]-2-oxo-5- acetate oxazolidinyl]methyl]-thioacetamide 126 (S)-N-[[3-[3-Fluoro-4-[4- P-93 Z (a) (methoxyacetyl)-1- piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide 127 (S)-N-[[3-[3-Fluoro-4-[4- P-93 Z (b) (methoxyacetyl)-1- piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide 128 (S)-N-[[3-[3-Fluoro-4-[4- P-93 Z (c) (methoxyacetyl)-1- piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- methylpropanethioamide 129 (S)-N-[[3-[3-Fluoro-4-[4- P-93 Z (d) (methoxyacetyl)-1- piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- butanethioamide 130 (S)-N-[[3-[3-Fluoro-4-[4- P-93 Z (e) (methoxyacetyl)-1- (methoxyacetyl)-1- piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-3- methylbutanethioamide 131 (S)-N-[[3-[3-Fluoro-4-[4- P-93 Z (f) (methoxyacetyl)-1- piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylbutanethioamide 132 (S)-N-[[3-[3-Fluoro-4-[4- P-93 Z (g) (methoxyacetyl)-1- piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-3, 3- dimethylbutanethioamide 133 (S)-N-[[3-[3-Fluoro-4-[4- P-93 Z (h) (methoxyacetyl)-1- piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclobutanecarbothioamide 134 (S)-N-[[3-[3-Fluoro-4-[4- P-93 Z (i) (methoxyacetyl)-1- piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopentanecarbothioamide 135 (S)-N-[[3-[3-Fluoro-4-[4- P-93 Z (j) (methoxyacetyl)-1- piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclohexanecarbothioamide 136 (S)-N-[[3-[3-Fluoro-4-[4- P-93 Z (k) (methoxyacetyl)-1- piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclopropylethanethioamide 137 (S)-N-[[3-[3-Fluoro-4-[4- P-93 Z (l) (methoxyacetyl)-1-piperazinyl] phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclobutylethanethioamide 138 (S)-N-[[3-[3-Fluoro-4-[4- P-93 Z (m) (methoxyacetyl)-1-piperazinyl] phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclopentylethanethioamide 139 (S)-N-[[3-[3,5-Difluoro-[4-[4- P-94 Ethyl (methoxyacetyl)-1- dithio- piperazinyl]phenyl]-2-oxo-5- acetate oxazolidinyl]methyl]- thioacetamide 140 (S)-N-[[3-[3,5-Difluoro-[4-[4- P-94 Z (a) (methoxyacetyl)-1- piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-propanethioamide 141 (S)-N-[[3-[3, 5-Difluoro-[4-[4- P-94 Z (b) (methoxyacetyl)-1- piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide 142 (S)-N-[[3-[3,5-Difluoro-[4-[4- P-94 Z (c) (methoxyacetyl)-1- piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothioamide 143 (S)-N-[[3-[4-[4-(methoxyacetyl)-1- P-95 Ethyl piperazinyl]phenyl]-2-oxo-5-oxazolidinyl] dithio- methyl]thioacetamide acetate 144 (S)-N-[[3-[4-[4-(methoxyacetyl)-1- P-95 Z (a) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl] methyl]propanethioamide 145 (S)-N-[[3-[4-[4-(methoxyacetyl)-1- P-95 Z (b) piperazinyl]phenyl]-2-oxo-5-oxazolidinyl] methyl]-2-methylpropane-thioamide 146 (S)-N-[[3-[4-[4-(methoxyacetyl)-1- P-95 Z (c) piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl] cyclopropanecarbothioamide 147 (S)-N-[[3-[3-Fluoro-4-[4- P-96 Ethyl (cyanoacetyl)-1-piperazinyl]- dithio- phenyl]-2-oxo-5-oxazolidinyl]methyl] acetate thioacetamide 148 (S)-N-[[3-[3-Fluoro-4-[4- P-96 Z (a) (cyanoacetyl)-1-piperazinyl]- phenyl]-2-oxo-5-oxazolidinyl]methyl] propanethioamide 149 (S)-N-[[3-[3-Fluoro-4-[4-(cyanoacetyl)- P-96 Z (a) 1-piperazinyl]- phenyl]-2-oxo-5-oxazolidinyl]methyl]- 2-methyl-propanethioamide 150 (S)-N-[[3-[3-Fluoro-4-[4-(cyanoacetyl)- P-96 Z (b) 1-piperazinyl]- phenyl]-2-oxo-5-oxazolidinyl]methyl] cyclopropane-carbothioamide 151 (S)-N-[[3-[3,5-Difluoro-4-[4- P-97 Ethyl (cyanoacetyl)-1- dithio- piperazinyl]phenyl]-2-oxo-5- acetate oxazolidinyl]- methyl]thioacetamide 152 (S)-N-[[3-[3,5-Difluoro-4-[4- P-97 Z (a) (cyanoacetyl)-1- piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]-methyl]propanethioamide 153 (S)-N-[[3-[3,5-Difluoro-4-[4- P-97 Z (b) (cyanoacetyl)-1- piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide 154 (S)-N-[[3-[3,5-Difluoro-4-[4- P-97 Z (c) (cyanoacetyl)-1- piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]- methyl]cyclopropanecarbothioamide 155 (S)-N-[[3-[4-[4-(Cyanoacetyl)-1- P-98 Ethyl piperazinyl]phenyl]-2-oxo-5- dithio- oxazolidinyl]mazinyl]phenyl]-2- dithio- oxo-5-oxazolidinyl]methyl] acetate thioacetamide 156 (S)-N-[[3-[4-[4-(Cyanoacetyl)-1- P-98 Z (a) piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]propanethioamide 157 (S)-N-[[3-[4-[4-(Cyanoacetyl)-1- P-98 Z (b) piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide 158 (S)-N-[[3-[4-[4-(Cyanoacetyl)-1- P-98 Z (c) piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl] cycopropanecarbothioamide 159 (S)-N-[[3-[3-Fluoro-4-[4- P-99 Ethyl (acetoxyacetyl)-1- dithio- piperazinyl]phenyl]-2-oxo-5- acetate oxazolidinyl]methyl]- thioacetamide 160 (S)-N-[[3-[3-Fluoro-4-[4- P-99 Z (a) (acetoxyacetyl)-1- piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-propanethioamide 161 (S)-N-[[3-[3-Fluoro-4-[4- P-99 Z (b) (acetoxyacetyl)-1- piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide 162 (S)-N-[[3-[3-Fluoro-4-[4- P-99 Z (c) (acetoxyacetyl)-1-piperazinyl] phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothioamide 163 (S)-N-[[3-[3-Fluoro-4-[4- P-99 Z (d) (acetoxyacetyl)-1- piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-butanethioamide 164 (S)-N-[[3-[3-Fluoro-4-[4- P-99 Z (e) (acetoxyacetyl)-1-piperazinyl]phenyl]- 2-oxo-5-oxazolidinyl]methyl]-3- methylbutanethioamide 165 (S)-N-[[3-[3-Fluoro-4-[4- P-99 Z (f) (acetoxyacetyl)-1-piperazinyl]phenyl]- 2-oxo-5-oxazolidinyl]methyl]-2- methylbutanethioamide 166 (S)-N-[[3-[3-Fluoro-4-[4- P-99 Z (g) (acetoxyacetyl)-1- piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-3,3- dimethylbutanethioamide 167 (S)-N-[[3-[3-Fluoro-4-[4- P-99 Z (h) (acetoxyacetyl)-1- piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclobutanecarbothioamide 168 (S)-N-[[3-[3-Fluoro-4-[4- P-99 Z (i) (acetoxyacetyl)-1- piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopentanecarbothioamide 169 (S)-N-[[3-[3-Fluoro-4-[4- P-99 Z (j) (acetoxyacetyl)-1- piperazinyl]phenyl]-2-oxo- 5-oxazolidinyl]methyl]- cyclohexanecarbothioamide 170 (S)-N-[[3-[3-Fluoro-4-[4- P-99 Z (k) (acetoxyacetyl)-1- piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclopropylethanethioamide 171 (S)-N-[[3-[3-Fluoro-4-[4- P-99 Z (l) (acetoxyacetyl)-1- piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclobutylethanethioamide 172 (S)-N-[[3-[3-Fluoro-4-[4- P-99 Z (m) (acetoxyacetyl)-1- piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclopentylethanethioamide 173 (S)-N-[[3-[3,5-Difluoro-4-[4- P- Ethyl (acetoxyacetyl)-1- 100 dithio- piperazinyl]phenyl]-2-oxo-5- acetate oxazolidinyl]methyl]- thioacetamide 174 (S)-N-[[3-[3,5-Difluoro-4-[4- P- Z (a) (acetoxyacetyl)-1- 100 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide 175 (S)-N-[[3-[3,5-Difluoro-4-[4- P- Z (b) (acetoxyacetyl)-1- 100 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide 176 (S)-N-[[3-[3,5-Difluoro-4-[4- P- Z (c) (acetoxyacetyl)-1- 100 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothioamide 177 (S)-N-[[3-[4-[4-(Acetoxyacetyl)-1- P- Ethyl piperazinyl]phenyl]-2-oxo-5- 100 dithio- oxazolidinyl]methyl]thioacetamide acetate 178 (S)-N-[[3-[4-[4-(Acetoxyacetyl)-1- P- Z (a) piperazinyl]phenyl]-2-oxo-5- 101 oxazolidinyl]methyl]propanethioamide 179 (S)-N-[[3-[4-[4-(Acetoxyacetyl)-1- P- Z (b) piperazinyl]phenyl]-2-oxo-5- 101 oxazolidinyl]methyl]-2- methylpropane-thioamide 180 (S)-N-[[3-[4-[4-(Acetoxyacetyl)-1- P- Z (c) piperazinyl]phenyl]-2-oxo-5- 101 oxazolidinyl]methyl] cyclopropanecarbo-thioamide 181 (S)-N-[[3-[3-Fluoro-4-[4- P- Ethyl (benzyloxyacetyl)-1- 102 dithio- piperazinyl]phenyl]-2-oxo-5- acetate oxazolidinyl]methyl]- thioacetamide 182 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (a) (benzyloxyacetyl)-1- 102 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-propanethioamide 183 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (b) (benzyloxyacetyl)-1- 102 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide 184 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (c) (benzyloxyacetyl)-1-piperazinyl] 102 phenyl]-2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothioamide 185 (S)-N-[[3-[3,5-Difluoro-4-[4- P- Ethyl (benzyloxyacetyl)-1- 103 dithio- piperazinyl]phenyl]-2-oxo-5- acetate oxazolidinyl]methyl]- thioacetamide 186 (S)-N-[[3-[3,5-Difluoro-4-[4- P- Z (a) (benzyloxyacetyl)-1- 103 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-propanethioamide 187 (S)-N-[[3-[3,5-Difluoro-4-[4- P- Z (b) (benzyloxyacetyl)-1- 103 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide 188 (S)-N-[[3-[3,5-Difluoro-4-[4- P- Z (c) (benzyloxyacetyl)-1- 103 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothioamide 189 (S)-N-[[3-[3-Fluoro-4-[4- P- Ethyl (methoxycarbonyl)-1- 105 dithio- piperazinyl]phenyl]-2-oxo-5- acetate oxazolidinyl]methyl]- thioacetamide 190 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (a) (methoxycarbonyl)-1- 105 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-propanethioamide 191 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (b) (methoxycarbonyl)-1- 105 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide 192 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (c) (methoxycarbonyl)-1- 105 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothioamide 193 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (d) (methoxycarbonyl)-1- 105 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-butanethioamide 194 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (e) (methoxycarbonyl)-1- 105 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-3- methylbutanethioamide 195 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (f) (methoxycarbonyl)-1- 105 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylbutanethioamide 196 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (g) (methoxycarbonyl)-1- 105 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-3, 3-dimethylbutanethioamide 197 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (h) (methoxycarbonyl)-1- 105 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclobutanecarbothioamide 198 (S)-N-[[ 3-[3-Fluoro-4-[4- P- Z (i) (methoxycarbonyl)-1- 105 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopentanecarbothioamide 199 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (j) (methoxycarbonyl)-1- 105 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclohexanecarbothioamide 200 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (k) (methoxycarbonyl)-1- 105 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclopropylethanethioamide 201 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (l) (methoxycarbonyl)-1- 105 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclobutylethanethioamide 202 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (m) (methoxycarbonyl)-1- 105 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclopentylethanethioamide 203 (S)-N-[[3-[3,5-Difluoro-4-[4- P- Ethyl (methoxycarbonyl)-1- 106 dithio- piperazinyl]phenyl]-2-oxo-5- acetate oxazolidinyl]methyl]- thioacetamide 204 (S)-N-[[3-[3,5-Difluoro-4-[4- P- Z (a) (methoxycarbonyl)-1- 106 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide 205 (S)-N-[[3-[3,5-Difluoro-4-[4- P- Z (b) (methoxycarbonyl)-1- 106 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide 206 (S)-N-[[3-[3,5-Difluoro-4-[4- P- Z (c) (methoxycarbonyl)-1- 106 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothioamide 207 (S)-N-[[3-[4-[4- P- Ethyl (methoxycarbonyl)-1- 107 dithio- piperazinyl]phenyl]-2-oxo-5- acetate oxazolidinyl]methyl]- thioacetamide 208 (S)-N-[[3-[4-[4- P- Z (a) (methoxycarbonyl)-1- 107 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide 209 (S)-N-[[3-[4-[4- P- Z (b) (methoxycarbonyl)-1- 107 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide 210 (S)-N-[[3-[4-[4- P- Z (c) (methoxycarbonyl)-1- 107 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothioamide 211 (S)-N-[[3-[3-Fluoro-4-[4- P- Ethyl (methanesulfonyl)-1- 108 dithio- piperazinyl]phenyl]-2-oxo-5- acetate oxazolidinyl]methyl]- thioacetamide; mp 197-198° C.; Anal, calcd for C₁₇H₂₃FN₄O₄S₂: C, 47.43; H, 5.39; N, 13.01; S, 14.89. Found: C, 47.25; H, 5.40; N, 12.82; S, 14.56. 212 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (a) (methanesulfonyl)-1- 108 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide; mp 207-208° C.; Anal. calcd for C₁₈H₂₅FN₄O₄S₂: C, 48.63; H, 5.67; N, 12.60; S, 14.42. Found: C, 48.51; H, 5.59; N, 12.52; S, 14.09. 213 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (b) (methanesulfonyl)-1- 108 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide; mp 204-206° C.; Anal. calcd for C₁₉H₂₇FN₄O₄S₂: C, 49.76; H, 5.93; N, 12.22; S, 13.98. Found: C, 49.63; H, 5.92; N, 14.14; S, 13.91. 214 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (a) (methanesulfonyl)-1- 108 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothioamide; Anal. calcd for C₁₉H₂₅FN₄O₄S₂: C, 49.98; H, 5.52; N, 12.27; S, 14.04. Found: C, 49.42; H, 5.50; N, 12.08; S, 13.80. 215 (S)-N-[[3-[3,5-Difluoro-4-[4- P- Ethyl (methanesulfonyl)-1- 109 dithio- piperazinyl]phenyl]-2-oxo-5- acetate oxazolidinyl]methyl]- thioacetamide 216 (S)-N-[[3-[3,5-Difluoro-4-[4- (methanesulfonyl)-1- piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide 217 (S)-N-[[3-[3,5-Difluoro-4-[4- (methanesulfonyl)-1- piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide 218 (S)-N-[[3-[3,5-Difluoro-4-[4- (methanesulfonyl)-1- piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothioamide 219 (S)-N-[[3-[4-[4- (methanesulfonyl)-1- piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- thioacetamide 220 (S)-N-[[3-[4-[4- (methanesulfonyl)-1- piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide 221 (S)-N-[[3-[4-[4- (methanesulfonyl)-1- piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide 222 (S)-N-[[3-[4-[4- (methanesulfonyl)-1- piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothioamide 223 (S)-N-[[3-[3-Fluoro-4-[4- (ethanesulfonyl)-1- piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- thioacetamide 224 (S)-N-[[3-[3-Fluoro-4-[4- (ethanesulfonyl)-1- piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide 225 (S)-N-[[3-[3-Fluoro-4-[4- P- (ethanesulfonyl)-1- 111 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide 226 (S)-N-[[3-[3-Fluoro-4-[4- P- (ethanesulfonyl)-1- 111 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothioamide 227 (S)-N-[[3-[3,5-Difluoro-4-[4- P- (ethanesulfonyl)-1- 112 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- thioacetamide 228 (S)-N-[[3-[3,5-Difluoro-4-[4- P- (ethanesulfonyl)-1- 112 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide 229 (S)-N-[[3-[3,5-Difluoro-4-[4- P- (ethanesulfonyl)-1- 112 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide 230 (S)-N-[[3-[3,5-Difluoro-4-[4- P- (ethanesulfonyl)-1- 112 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothioamide 231 (S)-N-[[3-[4-[4-(ethanesulfonyl)-1- P- piperazinyl]phenyl]-2-oxo-5- 113 oxazolidinyl]methyl]thioacetamide 232 (S)-N-[[3-[4-[4-(ethanesulfonyl)-1- P- piperazinyl]phenyl]-2-oxo-5- 113 oxazolidinyl]methyl]propanethioamide 233 (S)-N-[[3-[4-[4-(ethanesulfonyl)-1- P- piperazinyl]phenyl]-2-oxo-5- 113 oxazolidinyl]methyl]-2- methylpropane-thioamide 234 (S)-N-[[3-[4-[4-(ethanesulfonyl)-1- P- Z (c) piperazinyl]phenyl]-2-oxo-5- 113 oxazolidinyl]methyl] cyclopropanecarbothioamide 235 (S)-N-[[3-[3-Fluoro-4-[4- P- Ethyl (chloromethanesulfonyl)-1- 114 dithio- piperazinyl]phenyl]-2-oxo-5- acetate oxazolidinyl]methyl]- thioacetamide 236 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (a) (chloromethanesulfonyl)-1- 114 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-propanethioamide 237 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (b) (chloromethanesulfonyl)-1- 114 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide 238 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (c) (chloromethanesulfonyl)-1- 114 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothioamide 239 (S)-N-[[3-[3,5-Difluoro-4-[4- P- Ethyl (chloromethanesulfonyl)- 115 dithio- 1-piperazinyl]phenyl]-2-oxo-5- acetate oxazolidinyl]methyl]- thioacetamide 240 (S)-N-[[3-[3,5-Difluoro-4-[4- P- Z (a) (chloromethanesulfonyl)- 115 1-piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]propanethioamide 241 (S)-N-[[3-[3,5-Difluoro-4-[4- P- Z (b) (chloromethanesulfonyl)-1- 115 piperazinyl]phenyl]- 2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 242 (S)-N-[[3-[3,5-Difluoro-4-[4- P- Z (c) (chloromethanesulfonyl)-1- 115 piperazinyl]phenyl]- 2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothioamide 243 (S)-N-[[3-[4-[4- P- Ethyl (chloromethanesulfonyl)-1- 116 dithio- piperazinyl]phenyl]-2-oxo-5- acetate oxazolidinyl]methyl]- thioacetamide 244 (S)-N-[[3-[4-[4- P- Z (a) (chloromethanesulfonyl)-1- 116 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-propanethioamide 245 (S)-N-[[3-[4-[4- P- Z (b) (chloromethanesulfonyl)-1- 116 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide 246 (S)-N-[[3-[4-[4- P- Z (c) (chloromethanesulfonyl)-1- 116 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothioamide 247 (S)-N-[[3-[3-Fluoro-4-[4- P- Ethyl (cyanomethane-sulfonyl)-1- 117 dithio- piperazinyl]phenyl]-2-oxo-5- acetate oxazolidinyl]methyl]thioacetamide 248 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (a) (cyanomethane-sulfonyl)-1- 117 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-propanethioamide 249 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (b) (cyanomethane-sulfonyl)-1- 117 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide 250 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (c) (cyanomethane-sulfonyl)-1- 117 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothioamide 251 (S)-N-[[3-[3,5-Difluoro-4-[4- Ethyl (cyanomethane-sulfonyl)-1- dithio- piperazinyl]phenyl]-2 acetate -oxo-5- oxazolidinyl]methyl]thioacetamide 252 (S)-N-[[3-[3,5-Difluoro-4-[4- P- Z (a) (cyanomethane-sulfonyl)-1- 118 piperazinyl]phenyl]- 2-oxo-5-oxazolidinyl]- methyl]propanethioamide 253 (S)-N-[[3-[3,5-Difluoro-4-[4- P- Z (b) (cyanomethane-sulfonyl)-1- 118 piperazinyl]phenyl]- 2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 254 (S)-N-[[3-[3,5-Difluoro-4-[4- P- Z (c) (cyanomethane-sulfonyl)-1- 118 piperazinyl]phenyl]- 2-oxo-5-oxazolidinyl]methyl]- cyclopropanecarbothioamide 255 (S)-N-[[3-[4-[4- P- Ethyl (Cyanomethanesulfonyl)-1- 119 dithio- piperazinyl]phenyl]-2-oxo-5- acetate oxazolidinyl]methyl]thioacetamide 256 (S)-N-[[3-[4-[4- P- Z (a) (Cyanomethanesulfonyl)-1- 119 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl] propanethioamide 257 (S)-N-[[3-[4-[4- P- Z (b) (Cyanomethanesulfonyl)-1- 119 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide 258 (S)-N-[[3-[4-[4- P- Z (c) (Cyanomethanesulfonyl)-1- 119 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl] cyclopropanecarbo thioamide 259 (S)-N-[[3-[3-Fluoro-4-[4-(N- P- Ethyl methylsulfamoyl)-1- 120 dithio- piperazinyl]phenyl]-2-oxo-5- acetate oxazolidinyl]methyl]- thioacetamide 260 (S)-N-[[3-[3-Fluoro-4-[4-(N- P- Z (a) methylsulfamoyl)-1- 120 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide 261 (S)-N-[[3-[3-Fluoro-4-[4-(N- P- Z (b) methylsulfamoyl)-1- 120 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide 262 (S)-N-[[3-[3-Fluoro-4-[4-(N- P- Z (c) methylsulfamoyl)-1- 120 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothioamide 263 (S)-N-[[3-[3,5-Difluoro-4-[4-(N- P- Ethyl methylsulfamoyl)-1- 121 dithio- piperazinyl]phenyl]-2-oxo-5- acetate oxazolidinyl]methyl]thioacetamide 264 (S)-N-[[3-[3,5-Difluoro-4-[4-(N- P- Z (a) methylsulfamoyl)-1- 121 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide 265 (S)-N-[[3-[3,5-Difluoro-4-[4-(N- P- Z (b) methylsulfamoyl)-1- 121 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide 266 (S)-N-[[3-[3,5-Difluoro-4-[4-(N- P- Z (c) methylsulfamoyl)-1- 121 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothioamide 267 (S)-N-[[3-[4-[4-(N- P- Ethyl methylsulfamoyl)-1- 122 dithio- piperazinyl]phenyl]-2-oxo-5- acetate oxazolidinyl]methyl]- thioacetamide 268 (S)-N-[[3-[4-[4-(N- P- Z (a) methylsulfamoyl)-1- 122 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide 269 (S)-N-[[3-[4-[4-(N- P- Z (b) methylsulfamoyl)-1- 122 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide 270 (S)-N-[[3-[4-[4-(N- P- Z (c) methylsulfamoyl)-1- 122 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothioamide 271 (S)-N-[[3-[3-Fluoro-4-[4- P- Ethyl (N,N-dimethylsulfamoyl)-1- 123 dithio- piperazinyl]phenyl]-2-oxo-5- acetate oxazolidinyl]methyl]- thioacetamide 272 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (a) (N,N-dimethylsulfamoyl)-1- 123 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide 273 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (b) (N,N-dimethylsulfamoyl)-1- 123 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide 274 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (c) (N,N-dimethylsulfamoyl)-1- 123 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothioamide 275 (S)-N-[[3-[3,5-Difluoro-4-[4- P- Ethyl (N,N-dimethylsulfamoyl)-1- 124 dithio- piperazinyl]phenyl]- acetate 2-oxo-5-oxazolidinyl]methyl]- thioacetamide 276 (S)-N-[[3-[3,5-Difluoro-4-[4- P- Z (a) (N,N-dimethylsulfamoyl)-1- 124 piperazinyl]phenyl]- 2-oxo-5-oxazolidinyl]methyl]- propanethioamide 277 (S)-N-[[3-[3,5-Difluoro-4-[4- P- Z (b) (N,N-dimethylsulfamoyl)-1- 124 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide 278 (S)-N-[[3-[3,5-Difluoro-4-[4- P- Z (c) (N,N-dimethylsulfamoyl)-1- 124 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothioamide 279 (S)-N-[[3-[4-[4- P- Ethyl (N,N-dimethylsulfamoyl)-1- 125 dithio- piperazinyl]phenyl]-2-oxo-5- acetate oxazolidinyl]methyl]- thioacetamide 280 (S)-N-[[3-[4-[4- P- Z (a) (N,N-dimethylsulfamoyl)-1- 125 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide 281 (S)-N-[[3-[4-[4- P- Z (b) (N,N-dimethylsulfamoyl)-1- 125 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide 282 (S)-N-[[3-[4-[4- P- Z (c) (N,N-dimethylsulfamoyl)-1- 125 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothioamide 283 (S)-N-[[3-[3-Fluoro-4-[4- P- Ethyl (ethoxycarbonyl)-1- 126 dithio- piperazinyl]phenyl]-2-oxo-5- acetate oxazolidinyl]methyl]- thioacetamide 284 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (a) (ethoxycarbonyl)-1- 126 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide 285 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (b) (ethoxycarbonyl)-1- 126 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide 286 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (c) (ethoxycarbonyl)-1- 126 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothioamide 287 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (d) (ethoxycarbonyl)-1- 126 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- butanethioamide 288 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (e) (ethoxycarbonyl)-1- 126 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-3- methylbutanethioamide 289 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (f) (ethoxycarbonyl)-1- 126 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylbutanethioamide 290 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (g) (ethoxycarbonyl)-1- 126 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-3,3- dimethylbutanethioamide 291 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (h) (ethoxycarbonyl)-1- 126 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclobutanecarbothioamide 292 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (i) (ethoxycarbonyl)-1- 126 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopentanecarbothioamide 293 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (j) (ethoxycarbonyl)-1- 126 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclohexanecarbothioamide 294 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (k) (ethoxycarbonyl)-1- 126 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclopropylethanethioamide 295 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (l) (ethoxycarbonyl)-1- 126 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclobutylethanethioamide 296 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (m) (ethoxycarbonyl)-1- 126 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- cyclopentylethanethioamide 297 (S)-N-[[3-[3,5-Difluoro-4-[4- P- Ethyl (ethoxycarbonyl)-1- 127 dithio- piperazinyl]phenyl]-2-oxo-5- acetate oxazolidinyl]methyl]- thioacetmide 298 (S)-N-[[3-[3,5-Difluoro-4-[4- P- Z (a) (ethoxycarbonyl)-1- 127 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide 299 (S)-N-[[3-[3,5-Difluoro-4-[4- P- Z (b) (ethoxycarbonyl)-1- 127 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide 300 (S)-N-[[3-[3,5-Difluoro-4-[4- P- Z (c) (ethoxycarbonyl)-1- 127 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothioamide 301 (S)-N-[[3-[4-[4- P- Ethyl (ethoxycarbonyl)-1- 127 dithio- piperazinyl]- acetate phenyl]-2-oxo-5- oxazolidinyl]methyl] thioacetamide 302 (S)-N-[[3-[4-[4- P- Z (a) (ethoxycarbonyl)-1- 128 piperazinyl]- phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide 303 (S)-N-[[3-[4-[4- P- Z (b) (ethoxycarbonyl)-1- 128 piperazinyl]- phenyl]-2-oxo-5- oxazolidinyl]methyl]- 2-methylpropanethioamide 304 (S)-N-[[3-[4-[4- P- Z (c) (ethoxycarbonyl)-1- 128 piperazinyl]- phenyl]-2-oxo-5-oxazolidinyl] methyl]cyclopropane-carbothioamide 305 (S)-N-[[3-[3-Fluoro-4-(4- P- Ethyl sulfamoyl-1-piperazinyl)- 129 dithio- phenyl]-2-oxo-5-oxazolidinyl] acetate methyl]thioacetamide 306 (S)-N-[[3-[3-Fluoro-4-(4- P- Z (a) sulfamoyl-1-piperazinyl)- 129 phenyl]-2-oxo-5-oxazolidinyl] methyl]-propanethioamide 307 (S)-N-[[3-[3-Fluoro-4-(4- P- Z (b) sulfamoyl-1-piperazinyl)- 129 phenyl]-2-oxo-5-oxazolidinyl] methyl]-2-methylpropanethioamide 308 (S)-N-[[3-[3-Fluoro-4-(4- P- Z (c) sulfamoyl-1-piperazinyl)- 129 phenyl]-2-oxo-5-oxazolidinyl] methyl]-cyclopropanecarbothioamide 309 (S)-N-[[3-[3-Fluoro-4-(4- P- Z (d) sulfamoyl-1-piperazinyl)- 129 phenyl]-2-oxo-5- oxazolidinyl]methyl]butanethioamide 310 (S)-N-[[3-[3-Fluoro-4-(4-sulfamoyl-1- P- Z (e) piperazinyl)phenyl]-2-oxo-5- 129 oxazolidinyl]methyl]-3- methylbutanethioamide 311 (S)-N-[[3-[3-Fluoro-4-(4- P- Z (f) sulfamoyl-1-piperazinyl) 129 phenyl]-2-oxo-5-oxazolidinyl] methyl]-2-methylbutanethioamide 312 (S)-N-[[3-[3-Fluoro-4-(4- P- Z (g) sulfamoyl-1-piperazinyl)phenyl]- 129 2-oxo-5-oxazolidinyl]methyl]-3,3- dimethylbutanethioamide 313 (S)-N-[[3-[3-Fluoro-4-(4- P- Z (g) sulfamoyl-1-piperazinyl)phenyl]- 129 2-oxo-5-oxazolidinyl] methyl]cyclobutanecarbothioamide 314 (S)-N-[[3-[3-Fluoro-4-(4- P- Z (i) sulfamoyl-1-piperazinyl)phenyl]- 129 2-oxo-5-oxazolidinyl]methyl] cyclopentanecarbothioamide 315 (S)-N-[[3-[3-Fluoro-4-(4- P- Z (j) sulfamoyl-1-piperazinyl) 129 phenyl]-2-oxo-5- oxazolidinyl]methyl] cyclohexanecarbothioamide 316 (S)-N-[[3-[3-Fluoro-4-(4- P- Z (k) sulfamoyl-1-piperazinyl) 129 phenyl]-2-oxo-5-oxazolidinyl] methyl]-2-cyclopropylethane- thioamide 317 (S)-N-[[3-[3-Fluoro-4-(4- P- Z (l) sulfamoyl-1-piperazinyl)phenyl]- 129 2-oxo-5-oxazolidinyl] methyl]-2-cyclobutylethane- thioamide 318 (S)-N-[[3-[3-Fluoro-4-(4- P- Z (m) sulfamoyl-1-piperazinyl)phenyl]- 129 2-oxo-5-oxazolidinyl] methyl]-2-cyclopentylethane- thioamide 319 (S)-N-[[3-[3,5-Difluoro-4-(4- P- Ethyl sulfamoyl-1-piperazinyl)phenyl]- 130 dithio- 2-oxo-5-oxazolidinyl] acetate methyl]thioacetamide 320 (S)-N-[[3-[3,5-Difluoro-4-(4- P- Z (a) sulfamoyl-1-piperazinyl)phenyl]- 130 2-oxo-5-oxazolidinyl] methyl]propanethioamide 321 (S)-N-[[3-[3,5-Difluoro-4-(4- P- Z (b) sulfamoyl-1-piperazinyl)phenyl]- 130 2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 322 (S)-N-[[3-[3,5-Difluoro-4-(4- P- Z (c) sulfamoyl-1-piperazinyl)phenyl]- 130 2-oxo-5-oxazolidinyl]methyl] cyclopropanecarbothioamide 323 (S)-N-[[3-[4-(4-sulfamoyl-1- P- Ethyl piperazinyl)phenyl]-2-oxo-5- 131 dithio- oxazolidinyl]methyl] acetate thioacetamide 324 (S)-N-[[3-[4-(4-sulfamoyl-1- P- Z (a) piperazinyl)phenyl]-2-oxo-5- 131 oxazolidinyl]methyl] propanethioamide 325 (S)-N-[[3-[4-(4-sulfamoyl-1- P- Z (b) piperazinyl)phenyl]-2-oxo-5- 131 oxazolidinyl]methy yl)phenyl]-2-oxo-5-oxazolidinyl] methyl]-2-methylpropanethioamide 326 (S)-N-[[3-[4-(4-sulfamoyl-1- P- Z (c) piperazinyl)phenyl]-2-oxo-5- 131 oxazolidinyl]methyl] cyclopropanecarbothioamide 327 (S)-N-[[3-[3-Fluoro-4-[4- P- Ethyl (cyanomethyl)-1- 132 dithio- piperazinyl]phenyl]-2-oxo-5- acetate oxazolidinyl]methyl]thioacetamide 328 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (a) (cyanomethyl)-1- 132 piperazinyl]phenyl]-2-oxo-5 oxazolidinyl]methyl] propanethioamide 329 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (b) (cyanomethyl)-1- 132 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide 330 (S)-N-[[3-[3-Fluoro-4-[4- P- Z (c) (cyanomethyl)-1- 132 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl] cyclopropanecarbothioamide 331 (S)-N-[[3-[3,5-Difluoro-4-[4- P- Ethyl (cyanomethyl)-1- 133 dithio- piperazinyl]phenyl]-2-oxo-5- acetate oxazolidinyl]methyl]thioacetamide 332 (S)-N-[[3-[3,5-Difluoro-4-[4-( P- Z (a) cyanomethyl)-1- 133 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]propanethioamide 333 (S)-N-[[3-[3,5-Difluoro-4-[4 P- Z (b) cyanomethyl)-1- 133 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide 334 (S)-N-[[3-[3,5-Difluoro-4-[4- P- Z (c) (cyanomethyl)-1-piperazinyl] 133 phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothioamide 335 (S)-N-[[3-[4-[4-(cyanomethyl)-1- P- Ethyl piperazinyl]phenyl]-2-oxo-5- 134 dithio- oxazolidinyl]methyl]thioacetamide acetate 336 (S)-N-[[3-[4-[4-(cyanomethyl)-1- P- Z (a) piperazinyl]phenyl]-2-oxo-5- 134 oxazolidinyl]methyl]propanethioamide 337 (S)-N-[[3-[4-[4-(cyanomethyl)-1- P- Z (b) piperazinyl]phenyl]-2-oxo-5- 134 oxazolidinyl]methyl]-2- methylpropanethioamide 338 (S)-N-[[3-[4-[4-(cyanomethyl)-1- piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl] cyclopropanecarbothioamide 339 (S)-N-[[3-[3-Fluoro-4-[4-(2- P- Ethyl fluoroethyl)-1- 135 dithio- piperazinyl]phenyl]-2-oxo-5- acetate oxazolidinyl]methyl]thioacetamide 340 (S)-N-[[3-[3-Fluoro-4-[4-(2- P- Z (a) fluoroethyl)-1- 135 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]propanethioamide 341 (S)-N-[[3-[3-Fluoro-4-[4-(2- P- Z (b) fluoroethyl)-1- 135 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide 342 (S)-N-[[3-[3-Fluoro-4-[4-(2- P- Z (c) fluoroethyl)-1- 135 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothioamide 343 (S)-N-[[3-[3,5-Difluoro-4-[4-(2- P- Ethyl fluoroethyl)-1- 136 dithio- piperazinyl]phenyl]-2-oxo-5- acetate oxazolidinyl]methyl]- thioacetamide 344 (S)-N-[[3-[3,5-Difluoro-4-[4- P- Z (a) (2-fluoroethyl)-1- 136 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl] propanethioamide 345 (S)-N-[[3-[3,5-Difluoro-4-[4- P- Z (b) (2-fluoroethyl)-1- 136 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]-2- methylpropanethioamide 346 (S)-N-[[3-[3,5-Difluoro-4-[4- P- Z (c) (2-fluoroethyl)-1- 136 piperazinyl]phenyl]-2-oxo-5- oxazolidinyl]methyl]- cyclopropanecarbothioamide 347 (S)-N-[[3-[4-[4-(2-fluoroethyl)-1- P- Ethyl piperazinyl]phenyl]- 137 dithio- 2-oxo-5-oxazolidinyl]methyl] acetate thioacetamide 348 (S)-N-[[3-[4-[4-(2-fluoroethyl)-1- P- Z (a) piperazinyl]phenyl]- 137 2-oxo-5-oxazolidinyl]methyl] propanethioamide 349 (S)-N-[[3-[4-[4-(2-fluoroethyl)-1- P- Z (b) piperazinyl]phenyl]- 137 2-oxo-5-oxazolidinyl]methyl]-2- methylpropanethioamide 350 (S)-N-[[3-[4-[4-(2-fluoroethyl)-1- P- Z (c) piperazinyl]phenyl]-2-oxo-5- 137 oxazolidinyl]methyl] cyclopropane-carbothioamide 351 (S)-N-[[3-[3-Fluoro-4-(4-formyl- P- Ethyl 1-piperazinyl)phenyl]-2-oxo-5- 138 dithio- oxazolidinyl]methyl]thioacetamide; acetate Anal calcd for C₁₇H₂₁FN₄O₃S: C, 53.67; H, 5.56; N, 14.73; S, 8.43. Found: C, 53.14; H, 5.42; N, 14.25; S, 8.18. 352 (S)-N-[[3-[3-Fluoro-4-(4-formyl- P- Z (a) 1-piperazinyl)phenyl]-2-oxo-5- 138 oxazolidinyl]methyl] propanethioamide; mp 166-167° C.; Anal. calcd for C₁₈H₂₃FN₄O₃S: C, 54.81; H, 5.88; N, 14.20; S, 8.13. Found: C, 54.83; H, 6.00; N, 14.12; S, 7.96. 353 (S)-N-[[3-[3-Fluoro-4-(4-formyl- P- Z (b) 1-piperazinyl)phenyl]-2-oxo-5- 138 oxazolidinyl]methyl]-2- methylpropane-thioamide; mp 157-158° C.: Anal. calcd for C₁₉H₂₅FN₄O₃S: C, 55.87, H, 6.17; N, 13.72; S, 7.85. Found: C, 55.67; H, 6.19; N, 13.50; S, 7.70. 354 (S)-N-[[3-[3-Fluoro-4-(4-formyl-1- P- Z (c) piperazinyl)phenyl]-2-oxo-5- 138 oxazolidinyl]methyl] cyclopropane-carbothioamide; mp 178-179° C.; Anal. calcd for C₁₉H₂₃FN₄O₃S: C, 56.14; H, 5.70; N, 13.78; S, 7.89. Found: C, 56.13; H, 5.64; N, 13.64; S. 7.75. 355 (S)-N-[[3-[3,5-Difluro-4-(4- P- Ethyl formyl-1-piperazinyl)- 139 dithio- phenyl]-2-oxo-5- acetate oxazolidinyl]methyl] thioacetamide 356 (S)-N-[[3-[3,5-Difluro-4-(4- P- Z (a) formyl-1-piperazinyl)- 139 phenyl]-2-oxo-5- oxazolidinyl]methyl]- propanethioamide 357 (S)-N-[[3-[3,5-Difluro-4-(4- P- Z (b) formyl-1-piperazinyl)- 139 phenyl]-2-oxo-5- oxazolidinyl]methyl]- 2-methyl-propanethioamide 358 (S)-N-[[3-[3,5-Difluro-4-(4- P- Z (c) formyl-1-piperazinyl)- 139 phenyl]-2-oxo-5- oxazolidinyl]methyl] cyclo-propanecarbothioamide 359 (S)-N-[[3-[4-(4-formyl-1- P- Ethyl piperazinyl)phenyl]-2-oxo-5- 140 dithio- oxazolidinyl]methyl] acetate thioacetamide 360 (S)-N-[[3-[4-(4-formyl-1- P- Z (a) piperazinyl)phenyl]-2-oxo-5- 140 oxazolidinyl]methyl] propanethioamide 361 (S)-N-[[3-[4-(4-formyl-1- P- Z (b) piperazinyl)phenyl]-2-oxo-5- 140 oxazolidinyl]methyl]-2- methylpropanethioamide 362 (S)-N-[[3-[4-(4-formyl-1- P- Z (c) piperazinyl)phenyl]-2-oxo-5- 140 oxazolidinyl]methyl] cyclopropane-carbothioamide Isothiocyanate Example Corresponding No. Product to Amine No. Amine 363 (S)-N-[[3-[3-Fluoro-4-(4- acetyl-1- piperazinyl)phenyl]-2- oxo-5-oxazolidinyl]- methyl]-1- azetidinecarbothioamide 364 (S)-N-[[3-[3-Fluoro-4-[4- (methoxyacetyl)-1- piperazinyl]phenyl]-2- oxo-5-oxazolidinyl] methyl]-1- azetidinecarbothioamide 365 (S)-N-[[3-[3-Fluoro-4-[4- (acetoxyacetyl)-1- piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]- methyl]-1- azetidinecarbothioamide 366 (S)-N-[[3-[3-Fluoro-4-[4- (methoxycarbonyl)-1- piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]- methyl]-1- azetidinecarbothioamide 367 (S)-N-[[3-[3-Fluoro-4-[4- (ethoxycarbonyl)-1- piperazinyl]phenyl]-2- oxo-5-oxazolidinyl]- methyl]-1- azetidinecarbothioamide 368 (S)-N-[[3-[3-Fluoro-4- (4-sulfamoyl-1- piperazinyl)phenyl]-2- oxo-5-oxazolidinyl]- methyl]-1- azetidinecarbothioamide

EXAMPLE 369

[0671] (5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H) yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide, Thiazepine S-oxide TABLE H Dithioester Example (from No. Compound Amine Preparation Z) 370 (5S)-N-[[3-[3- Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl))- phenyl]-2-oxo-5- oxazolidinyl]meth yl]- propanethioamide, thiazepine S- oxide

Z (a) 371 S)-N-[[3-[3- Same as above Z (b) Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl))- phenyl]-2-oxo-5- oxazolidinyl]meth yl]-2- methylpropanethio — amide, thiazepine S- oxide. 372 (5S)-N-[[3-[3- Same as above Z (c) Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl))- phenyl]-2-oxo-5- oxazolidinyl]meth yl]- cyclopropanecarbo thio- amide, thiazepine S- oxide. 373 (5S)-N-[[3-[3- Same as above Z (d) Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl))- phenyl]-2-oxo-5- oxazolidinyl]meth yl]- butanethioamide, thiazepine S- oxide 374 (5S)-N-[[3-[3- Same as above Z (e) Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl))- phenyl]-2-oxo-5- oxazolidinyl]methy 1]-3- methylbutanethioam ide, thiazepine S-oxide 375 (5S)-N-[[3-[3- Same as above Z (f) Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl))- phenyl]-2-oxo-5- oxazolidinyl]methy 1]-2- methylbutanethioam ide, thiazepine S-oxide 376 (5S)-N-[[3-[3- Same as above Z (g) Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl))- phenyl]-2-oxo-5- oxazolidinyl]methy 1]- 3,3- dimethylbutanethio — amide, thiazepine S- oxide 377 (5S)-N-[[3-[3- Same as above Z (h) Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl))- phenyl]-2-oxo-5- oxazolidinyl]methy 1]- cyclobutanecarboth io- amide, thiazepine S- oxide 378 (5S)-N-[[3-[3- Same as above Z (i) Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl))- phenyl]-2-oxo-5- oxazolidinyl]methy 1]-1- cyclopentanecarbot hio- amide, thiazepine oxide 379 (5S)-N-[[3-[3- Same as above Z (j) Fluoro-4 - (tetrahydro-1,4- thiazepin-4(5H)- yl))- phenyl]-2-oxo-5- oxazolidinyl]meth yl]- cyclohexanecarbot hio- amide, thiazepine oxide 380 (5S)-N-[[3-[3- Same as above Z (k) Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl))- phenyl]-2-oxo-5- oxazolidinyl]meth yl]-2- cyclopropylethane thio- amide, thiazepine S- oxide 381 (5S)-N-[[3-[3- Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl))- phenyl]-2-oxo-5- oxazolidinyl]meth yl]-2- cyclobutylethanet hio- amide, thiazepine S- oxide 382 (5S)-N-[[3-[3- Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl))- phenyl]-2-oxo-5- oxazolidinyl]meth yl]-2- cyclopentylethane thio- amide, thiazepine S- oxide

EXAMPLE 383

[0672] (5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4 (5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide, Thiazepine S-oxide TABLE I Dithioester Example (from No. Compound Amine Preparation Z) 384 (5S)-N-[[3-[3,5- Difluoro-4- (tetrahydro- 1,4-thiazepin- 4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]meth yl]- propanethioamide, thiazepine S- oxide

Z (a) 385 (5S)-N-[[3-[3,5- Same as above Z (b) Difluoro-4- (tetrahydro- 1,4-thiazepin- 4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]meth yl]-2- methylpropanethio- amide, thiazepine S- oxide 386 (5S)-N-[[3-[3,5- Same as above Z (c) Difluoro-4- (tetrahydro- 1,4-thiazepin- 4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]meth yl]- cyclopropanecarbo thio- amide, thiazepine S- oxide

EXAMPLE 387

[0673] (5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide, Thiazepine S-oxide. TABLE J Dithioester Example (from No. Compound Amine Preparation Z) 388 (5S)-N-[[3-[4- (Tetrahydro-1,4- yl))- phenyl]-2-oxo-5- thiazepin-4(5H)- oxazolidinyl]meth yl]- propanethioamide, thiazepine S- oxide

Z (a) 389 (5S)-N-[[3-[4- Same as above Z (b) (Tetrahydro-1,4- thiazepin-4(5H)- yl))- phenyl]-2-oxo-5- oxazolidinyl]meth yl]-2- methylpropanethio- amide, thiazepine S- oxide 390 (5S)-N-[[3-[4- Same as above Z (c) (Tetrahydro-1,4- thiazepin-4(5H)- yl))- phenyl]-2-oxo-5- oxazolidinyl]meth yl]- cyclopropanecarbo thio- amide, thiazepine S- oxide

EXAMPLE 391

[0674] (5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide, Thiazepine S,S-dioxide TABLE K Dithioester Example (from No. Compound Amine Preparation Z) 392 (5S)-N-[[3-[3- Fluoro-4- (4- thiomorpholinyl]- phenyl]-2-oxo-5- oxazolidinyl]met hyl]propanethioamide, thiazepine S,S- dioxide

Z (a) 393 (5S)-N-E[3-[3- Same as above Z (b) Fluoro-4- (4- thiomorpholinyl]- phenly]-2-oxo-5- oxazolidinyl]met hyl]-2- methylpropanethi o- amide, thiazepine S,S- dioxide 394 (5S)-N-[[3-[3- Same as above Z (c) Fluoro-4- (4- thiomorpholinyl]- phenyl]-2-oxo-5- oxazolidinyl]met hyl]- cyclopropanecarb othio- amide, thiazepine S,S- dioxide

EXAMPLE 395

[0675] (5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4 (5H yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide, Thiazepine S,S-dioxide TABLE L Dithioester Example (from No. Compound Amine Preparation Z) 396 (5S)-N-[[3-[3,5- Difluoro-4-(4- thiomorpholinyl]- phenyl]-2-oxo-5- oxazolidinyl]methy 1]- propanethioamide, thiazepine S,S- dioxide

Z (a) 397 (5S)-N-[[3-[3,5- Same as above Z (b) Difluoro-4-(4- thiomorpholinyl]- phenyl]-2-oxo-5- oxazolidinyl]methy 1]-2- methylpropanethio- amide, thiazepine S,S- dioxide 398 (5S)-N-[[3-[3,5- Same as above Z (c) Difluoro-4-(4- thiomorpholinyl]- phenyl]-2-oxo-5- oxazolidinyl]methy 1]- cyclopropanecarbot hio- amide, thiazepine S,S- dioxide

EXAMPLE 399

[0676] (5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide, Thiazepine S,S-dioxide TABLE M Dithioester Example (From No. Compound Amine Preparation Z) 400 (5S)-N-[[3-[4- (tetrahydro-1,4- thiazepin-4(5H)- yl))phenyl]-2-oxo- 5- ozolidinyl]- methyl]propanethio- amide, thiazepine S,S- dioxide

Z (a) 401 (5S)-N-[[3-[4- Same as above Z (b) (tetrahydro-1,4- thiazepin-4(5H)- yl))phenyl]-2-oxo- 5- oxazolidinyl]methy 1]-2- methylpropanethio- amide, thiazepine S,S- dioxide 402 (5S)-N-[[3-[4- Same as above Z (c) (tetrahydro-1,4- thiazepin-4(5H)- yl))phenyl]-2- oxo-5- oxazolidinyl]- methyl]cyclopropa ne- carbothioamide, thiazepine S,S- dioxide

EXAMPLE 403

[0677] (5S)-N-[[3-[3-Fluoro-4-(tetrahydro-1,4-thiazepin-4 (5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide TABLE N Dithioester Example (From No. Compound Amine Preparation Z) 404 (5S)-N-[[3-[3- Fluoro-4- (tetrahydro- 1,4- phenyl]-4(5H)- yl))- henY1J-2-oxo-5- oxazolidinyl]me thyl]- propanethio- amide

Z (a) 405 (5S)-N-[[3-[3- Same as above Z (b) Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl))- phenyl]-2-oxo-5- oxazolidinyl]meth yl]-2- methylpropanethio amide 406 (5S)-N-[[3-[3- Same as above Z (c) Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl))- phenyl]-2-oxo-5- oxazolidinyl]meth yl]- cyclopropanecarbo thio- amide 407 (5S)-N-[[3-[3- Same as above Z (d) Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl))- phenyl]-2-oxo-5- oxazolidinyl]meth yl]- butanethioamide 408 (5S)-N-[[3-[3- Same as above Z (e) Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl))- phenyl]-2-oxo-5- oxazolidinyl]meth yl]-3- methylbutanethioa mide 409 (5S)-N-[[3-[3- Same as above Z (f) Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl))- phenyl]-2-oxo-5- oxazolidinyl]meth yl]-2- methylbutanethioa mide 410 (5S)-N-[[3-[3- Same as above Z (g) Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl))- phenyl]-2-oxo-5- oxazolidinyl]meth yl]- 3,3- dimethylbutanethi o- amide 411 (5S)-N-[[3-[3- Same as above Z (h) Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl))- phenyl]-2-oxo-5- oxazolidinyl]meth yl]- cyclobutanecarbot hio- amide 412 (5S)-N-[[3-[3- Same as above Z (i) Fluoro-4- (tetrahydro-1, 4- thiazepin-4(5H)- yl))- phenyl]-2-oxo-5- oxazolidinyl]meth yl]- cyclopentanecarbo thio- amide 413 (5S)-N-[[3-[3- Same as above Z (j) Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl))- phenyl]-2-oxo-5- oxazolidinyl]meth yl]- cyclohexanecarbot hio- amide 414 (5S)-N-[[3-[3-5 Same as above Z (k) Fluoro- 4-(tetrahydro 1,4- thiazepin-4(5H)- yl))- phenyl]-2-oxo-5- oxazolidinyl]meth yl]-2- cyclopropylethane thio- amide 415 (5S)-N-[[3-[3- Same as above Z (l) Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl))- phenyl]-2-oxo-5- oxazolidinyl]meth yl]-2- cyclobutylethanet hio- amide 416 (5S)-N-[[3-[3- Same as above Z (m) Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl))- phenyl]-2-oxo-5- oxazolidinyl]methy 1]-2- cyclopentylethanet hioam ide

EXAMPLE 417

[0678] (5S)-N-[[3-[3,5-Difluoro-4-(tetrahydro-1,4-thiazepin-4 (5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide TABLE O Dithio Compound Example (from No. Compound Amine Preparation Z) 418 (5S)-N-[[3-[3,5- Difluoro-4- (tetrahydro- 1,4-thiazepin- phenyl]-2-oxo-5- oxazolidinyl]methy 1]- propanethioamide

Z (a) 419 (5S)-N-[[3-[3,5- Same as above Z (b) Difluoro-4- (tetrahydro- 1,4-thiazepin- 4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methy 1]-2- methylpropanethioa mide 420 (5S)-N-[[3-[3,5- Same as above Z (c) Difluoro-4- (tetrahydro- 1,4-thiazepin- 4(5H)-yl))- phenyl]-2-oxo-5- oxazolidinyl]methy 1]- cyclopropanecarbot hio- amide

EXAMPLE 421

[0679] (5S)-N-[[3-[4-(Tetrahydro-1,4-thiazepin-4(5H)-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide TABLE P Dithio Compound Example (from No. Compound Amine Preparation Z) 422 (5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)- yl))- phenyl]-2-oxo-5- oxazolidinyl]- methyl]propanethio- amide

Z (a) 423 (5S)-N-[[3-[4- Same as above Z (b) (Tetrahydro-1,4- thiazepin-4(5H)- yl))- phenyl]-2-oxo-5- oxazolidinyl]methy 1]-2- methylpropanethioa mide 424 (5S)-N-[[3-[4- Same as above Z (c) (Tetrahydro-1,4- thiazepin-4(5H)- yl))- phenyl]-2-oxo-5- oxazolidinyl]- methyl] cyclopropane- carbothioamide 425 (5S)-N-[[3-[3-Fluo ro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo-5 — oxazolidinyl]methy 1]-1- azetidinecarbothio amide, thiazepine S-oxide 426 (5S)-N-[[3-[3-Fluo ro-4- (tetrahydro-1,4 thiazepin-4(5H)- yl)phenyl]-2-oxo-5 oxazolidinyl]methy 1]-O- methylthiocarbamat e, thiazepine S-oxide 427 (5S)-N-[[3-[3,5- Difluoro-4- (tetrahydro- 1,4-thiazepin- 4(5H)- yl)phenyl]-2-oxo- 5- oxazolidinyl]meth yl]-1- azetidinecarbothi oamide, thiazepine 5- oxide 428 (5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo- 5- oxazolidinyl]meth yl]-1 azetidinecarbothi oamide, thiazepine S-oxide 429 (5S)-N-[[3-[3-Flu oro-4- (tetrahydro-1,4 thiazepin-4(5H)- yl)phenyl]-2-oxo- 5- oxazolidinyl]meth yl]-1- azetidinecarbothi oamide, thiazepine S,S-dioxide 430 (5S)-N-[[3-[3,5- Difluoro-4- (tetrahydro- 1,4-thiazepin- 4(5H)- yl)phenyl]-2-oxo- 5- oxazolidinyl]meth yl]-1- azetidinecarbothi oamide, thiazepine S,S- dioxide 431 (5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo- 5- oxazolidinyl]meth yl]-1- azetidinecarbothi oamide, thiazepine S,S- dioxide 432 (5S)-N-[[3-[3- Fluoro-4- (tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo- 5- oxazolidinyl]meth yl]-1- azetidinecarbothi oamide 433 (5S)-N-[[3-[3,5- Difluoro-4- (tetrahydro- 1,4-thiazepin- 4(5H)- yl)phenyl]-2- oxo-5- oxazolidinyl]met hyl]-1- azetidinecarboth ioamide 434 (5S)-N-[[3-[4- (Tetrahydro-1,4- thiazepin-4(5H)- yl)phenyl]-2-oxo- 5- oxazolidinyl]meth yl]-1- azetidinecarbothi oamide

EXAMPLE 435 (5R)-(−)-3-[3-Fluoro-4-(4-morpholinyl) phenyl]-2-oxo-5-oxazolidinecarboxamide—Method A

[0680]

[0681] Step 1: Preparation of (5R)-(−)-3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinecarboxylic Acid

[0682] A solution of benzyl 3-fluoro-4-(4-morpholinyl)phenylcarbamate (J. Med. Chem. 1996, 39(3), 673-679, 2.50 g, 7.57 mmol) in dry tetrahydrofuran (37.8 mL) at −78° C. under nitrogen was treated with n-butyllithium (1.6M in hexanes, 4.82 mL, 7.72 mmol) dropwise and stirred at −78° C. for 30 minutes. The cooling bath was removed and the mixture was allowed to slowly warm to −40° C., at which point potassium (2R)-glycidate (J. Org. Chem. 1992, 57(12), 3380-3387, 974 mg, 7.72 mmol) was added. After subsequent warming to ambient temperature, the resulting mixture was vigorously stirred for 2.75 days and then quenched with saturated aqueous ammonium chloride (20 mL), diluted with water (20 mL) and extracted with ethyl acetate (2×75 mL) to remove the remaining starting. The aqueous phase was adjusted to pH 2 with 1M aqueous hydrochloric acid, saturated with sodium chloride and extracted with methylene chloride (5×100 mL), and this combined organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the crude product. The product mixture was then chromatographed on a Flash 40M silica gel (90 g, 32-63 μm) cartridge, eluting with a gradient of acetonitrile/methylene chloride (10/90-40/60) containing 1% formic acid, and those fractions with an R_(f)=0.15 by TLC (acetonitrile/methylene chloride, 50/50+1% formic acid) are pooled and concentrated to give the title compound, ¹H NMR (400 MHz, DMSO-d₆) δ 13.7 (bs, 1H), 7.48 (dd, 1H), 7.23 (m, 1H), 7.05 (t, 1H), 5.17 (dd, 1H), 4.30 (t, 1H), 4.06 (dd, 1H), 3.73 (m, 4H), 2.96 (m, 4H); MS (ESI+) for C₁₄H₁₅FN₂O₅ m/z 311 (M+H)⁺; [α]²⁵ _(D)=−38° (c 0.94, DMSO).

[0683] Step 2: Preparation of (5R)-(−)-3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinecarboxamide

[0684] To a flame-dried flask containing (5R)-(−)-3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinecarboxylic acid (Step 1, 250 mg, 0.806 mmol) under nitrogen was added oxalyl chloride (4 mL) with stirring. The flask was capped with a drying tube, and the mixture was stirred at ambient temperature for 15 hours and then concentrated under reduced pressure to give the acid chloride intermediate [MS (ESI+) m/z 325 (M+H)⁺ observed for the methyl ester obtained by reaction of the acid chloride with methanol] which was used without further purification. This intermediate was then taken up in anhydrous tetrahydrofuran (8 mL) under nitrogen, cooled to 0° C., and ammonia (g) was bubbled in for 5 minutes. The resulting mixture was capped with a drying tube, stirred at ambient temperature for 1 hour, and then diluted with water (20 mL) and extracted with methanol/chloroform (10/90, 2×30 mL). The combined organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure, and the product mixture was recrystallized from ethyl acetate/hexane to give the title compound, mp 185-187° C. (decomp.); MS (ESI+) for C₁₄H₁₆FN₃O₄ m/z 310 (M+H)⁺; [α]²⁵ _(D)=−23° (c 0.89, DMSO).

EXAMPLE 436 (5R)-(−)-3-[3-Fluoro-4-(4-morpholinyl) phenyl]-N-methyl-2-oxo-5-oxazolidinecarboxamide

[0685]

[0686] Following the general procedure of EXAMPLE 435, Step 2, and making non-critical variations but substituting methylamine for ammonia, the title compound was obtained, mp 182-183° C. (decomp.); MS (ESI+) for C₁₅H₁₈FN₃O₄ m/z 324 (M+H)⁺; [α]²⁵ _(D)=−39° (c 0.92, DMSO)

EXAMPLE 437 (5R)-(−)-3-[3-Fluoro-4-(4-morpholinyl) phenyl]-N-allyl-2-oxo-5-oxazolidinecarboxamide

[0687]

[0688] To a flame-dried flask under nitrogen was added allylamine (0.60 mL, 8.05 mmol). The flask was cooled in an ice bath, and a solution of (5R)-3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinecarbonyl chloride (EXAMPLE 435, Step 2, 0.805 mmol theory) in anhydrous tetrahydrofuran (8.0 mL) was added. The resulting mixture was stirred under nitrogen for 2 hours, allowing the cooling bath to slowly expire, and was then diluted with water (10 mL) and extracted with methylene chloride (20 mL). The organic phase was washed with water (10 mL) and saline (10 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure, and the crude product was chromatographed on a Flash 40S silica gel (40 g, 32-63 μm) cartridge, eluting with a gradient of methanol/methylene chloride (0.5/99.5-2/98). Pooling and concentration of those fractions with an R_(f)=0.44 by TLC (methanol/chloroform, 5/95) provides the title compound, mp 167-169° C.; MS (ESI+) for C₁₇H₂₀FN₃O₄ m/z 350 (M+H)⁺; [α]²⁵ _(D)=−44° (c 0.94, DMSO).

EXAMPLE 438 (5R)-(−)-3-[3-Fluoro-4-(4-morpholinyl) phenyl]-N-propyl-2-oxo-5-oxazolidinecarboxamide

[0689]

[0690] Following the general procedure of EXAMPLE 437, and making non-critical variations but substituting propylamine for allylamine and triturating and filtering the final product from methanol/diethyl ether, the title compound was obtained, mp 165-167° C.; MS (ESI+) for C₁₇H₂₂FN₃O₄ m/z 352 (M+H)⁺; [α]²⁵ _(D)=−43° (c 1.02, DMSO).

EXAMPLE 439 (5R)-(−)-3-[3-Fluoro-4-(4-morpholinyl) phenyl]-N-methoxy-2-oxo-5-oxazolidinecarboxamide

[0691]

[0692] A mixture of (5R)-(−)-3-[3-fluoro-4-(4-morpholinyl) phenyl]-2-oxo-5-oxazolidinecarboxylic acid (EXAMPLE 1, Step 1, 150 mg, 0.483 mmol) and O-methylhydroxylamine hydrochloride (61 mg, 0.724 mmol) in tetrahydrofuran/water (1/1, 4.8 mL) was treated with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (278 mg, 1.45 mmol), and the resulting mixture was stirred at ambient temperature for 30 minutes and was then diluted with water (10 mL) and extracted with ethyl acetate (2×20 mL). The combined organic phase was washed with water (10 mL) and saline (10 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure, and the crude product was chromatographed on a Flash 40S silica gel (40 g, 32-63 μm) cartridge, eluting with methanol/methylene chloride (2.5/97.5). Pooling and concentration of those fractions with an R_(f)=0.53 by TLC (methanol/chloroform, 10/90) gives the title compound, mp 206-208° C. (decomp.); MS (ESI+) for C₁₅H₁₈FN₃O₅ m/z 340 (M+H)⁺; [α]²⁵ _(D)=−56° (c 0.92, DMSO).

EXAMPLE 440 (5R)-(−)-3-[3-Fluoro-4-(4-morpholinyl) phenyl]-N-hydroxy-2-oxo-5-oxazolidinecarboxamide

[0693]

[0694] Step 1: Preparation of (5R)-(−)-3-[3-fluoro-4-(4-morpholinyl)phenyl]-N-benzyloxy-2-oxo-5-oxazolidinecarboxamide

[0695] Following the general procedure of EXAMPLE 439, and making non-critical variations but substituting O-benzylhydroxylamine hydrochloride for O-methylhydroxylamine hydrochloride, the title compound was obtained, mp 191-193° C. (decomp.); MS (ESI+) for C₂₁H₂₂FN₃O₅ m/z 416 (M+H)⁺; [α]²⁵ _(D)=−46° (c 0.93, DMSO).

[0696] Step 2: Preparation of (5R)-(−)-3-[3-fluoro-4-(4-morpholinyl)phenyl]-N-hydroxy-2-oxo-5-oxazolidinecarboxamide

[0697] To a mixture of (5R)-(−)-3-[3-fluoro-4-(4-morpholinyl)phenyl]-N-benzyloxy-2-oxo-5-oxazolidinecarboxamide (Step 1, 300 mg, 0.722 mmol) in methanol (28.8 mL) was added 5% palladium-on-carbon (77 mg) under nitrogen. The resulting mixture was degassed and stirred under a hydrogen atmosphere (balloon) for 1 hour. The catalyst was then removed by filtration through Celite, rinsing with methanol (60 mL), and the filtrate was concentrated under reduced pressure. Trituration of this residue with (5% methanol/methylene chloride)/diethyl ether gives the title compound, mp 141-143° C.; MS (ESI+) for C₁₄H₁₆FN₃O₅ m/z 326 (M+H)⁺; [α]²⁵ _(D)=−70° (c 0.99, DMSO).

EXAMPLE 441 (5R)-(−)-3-[4-(3-Pyridyl)-3-fluorophenyl]-2-oxo-5-oxazolidinecarboxamide

[0698]

[0699] Step 1: Preparation of (5R)-(−)-3-[3-fluoro-4-iodophenyl]-5-hydroxymethyl-2-oxazolidinone

[0700] A solution of isobutyl 3-fluoro-4-iodophenylcarbamate (Org. Process Res. Dev. 2001, 5(1), 80-83, 5.00 g, 14.83 mmol) in dry tetrahydrofuran (59 mL) at −78° C. under nitrogen was treated with lithium hexamethyldisilazide (1.0M in tetrahydrofuran, 15.6 mL, 15.57 mmol) dropwise and stirred at −78° C. for 45 minutes. Then, (R)-glycidyl butyrate (2.21 mL, 15.57 mmol) was added dropwise, and the resulting mixture was stirred at −78° C. for 1 hour and at ambient temperature for 2.75 days. The reaction mixture was then quenched with saturated aqueous ammonium chloride (20 mL), diluted with water (20 mL) and the layers are separated. The aqueous phase was extracted with ethyl acetate (25 mL), and the combined organic phase was washed with water (25 mL) and saline (25 mL), dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The product mixture was then chromatographed on a Flash 40M silica gel (90 g, 32-63 μm) cartridge, eluting with a gradient of methanol/methylene chloride (1/99-2/98), and those fractions with an R_(f)=0.25 by TLC (methanol/chloroform, 5/95) are pooled and concentrated to give the title compound, mp 116-117° C.; MS (ESI+) for C₁₀H₉FINO₃ m/z 338 (M+H)⁺; [α]²⁵ _(D)=−41 (c 0.98, DMSO)

[0701] Step 2: Preparation of (−)-methyl (5R)-3-[3-fluoro-4-iodophenyl]-2-oxo-5-oxazolidinecarboxylate

[0702] A solution of (5R)-(−)-3-[3-fluoro-4-iodophenyl]-5-hydroxymethyl-2-oxazolidinone (Step 1, 7.61 g, 22.58 mmol) in acetone (150 mL) at −10° C. was treated with a mixture of CrO₃ (6.21 g, 62.1 mmol) in sulfuric acid (6M, 16.9 mL, 101 mmol) dropwise over 15 minutes. The resulting mixture was allowed to slowly warm to ambient temperature with vigorous stirring (slight exotherm to 35° C.) and was stirred for an additional 16 hours. The mixture was then treated with isopropanol (35 mL), diluted with saline (150 mL) and diethyl ether (150 mL), stirred until all solids are dissolved, and the layers are separated. The aqueous phase was extracted with diethyl ether (100 mL), and the combined organic phase was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give the crude carboxylic acid intermediate which was taken up in methanol (225 mL) and treated with concentrated sulfuric acid (8 drops). The resulting homogeneous mixture was stirred at ambient temperature for 20 hours and was then concentrated under reduced pressure to give the crude methyl ester product which was chromatographed on two Flash 40M 90 g silica gel (32-63 μm) cartridges, eluting with a gradient of ethyl acetate/heptane (20/80-40/60). Pooling and concentration of those fractions with an R_(f)=0.36 by TLC (ethyl acetate/hexane, 50/50) gives the title compound, mp 106-109° C.; MS (ESI+) for C₁₁H₉FINO₄ m/z 366 (M+H)⁺; [α]²⁵ _(D)=−30 (c 0.93, DMSO).

[0703] Step 3: Preparation of (5R)-(−)-3-[3-fluoro-4-iodophenyl]-2-oxo-5-oxazolidinecarboxamide

[0704] A solution of (−)-methyl (5R)-3-[3-fluoro-4-iodophenyl]-2-oxo-5-oxazolidinecarboxylate (Step 2, 6.23 g, 17.1 mmol) in acetonitrile (85 mL) was treated with concentrated ammonium hydroxide (85 mL), and the resulting mixture was stirred at ambient temperature for 1 hour. The mixture was then diluted with saline (100 mL) and extracted with methylene chloride (3×100 mL), and the combined organic phase was washed with saline (100 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was diluted with hot ethyl acetate (200 mL) and filtered to remove inorganic residue, and the filtrate was diluted with hexanes (300 mL). The resulting precipitate was isolated by filtration to give the title compound, mp 176-178° C.; MS (ESI+) for C₁₀H₈FIN₂O₃ m/z 351 (M+H)⁺; [α]²⁵ _(D)=−19 (c 0.97, DMSO).

[0705] Step 4: Preparation of 3-(trimethylstannyl)pyridine

[0706] A mixture of hexamethylditin (654 mg, 1.99 mmol), 3-bromopyridine (300 mg, 1.90 mmol) and bis(triphenylphosphine)palladium(II) chloride (40 mg, 0.057 mmol) in 1,4-dioxane (9.5 ml) was degassed, heated up to 90° C. under nitrogen, stirred at this temperature for 2.5 hours and at ambient temperature overnight, and was then concentrated under reduced pressure. The product mixture was chromatographed on a Flash 40S 40 g silica gel (32-63 μm) cartridge, eluting with ethyl acetate/heptane (20/80), and those fractions with an R_(f)=0.47 by TLC (ethyl acetate/hexane, 50/50) are pooled and concentrated to give the title compound (see Chem. Pharm. Bull. 1982, 30(5), 1731-1737 for characterization).

[0707] Step 5: Preparation of (5R)-(−)-3-[4-(3-pyridyl)-3-fluorophenyl]-2-oxo-5-oxazolidinecarboxamide

[0708] A mixture of (5R)-(−)-3-[3-fluoro-4-iodophenyl]-2-oxo-5-oxazolidinecarboxamide (Step 3, 422 mg, 1.21 mmol), 3-(trimethylstannyl)pyridine (Step 4, 350 mg, 1.45 mmol), tris(dibenzylideneacetone)dipalladium(0) (22 mg, 0.0242 mmol), triphenylarsine (59 mg, 0.194 mmol) and copper(I) iodide (9 mg, 0.0484 mmol) in N-methyl-2-pyrrolidinone (4.8 mL) under nitrogen was degassed, heated up to 50° C. and stirred at this temperature for 2 days, during which additional tris(dibenzylideneacetone)dipalladium(0) (22 mg, 0.0242 mmol), triphenylarsine (59 mg, 0.194 mmol) and copper(I) iodide (9 mg, 0.0484 mmol) are added. The resulting mixture was diluted with water (15 mL) and extracted with methylene chloride (3×20 mL), and the combined organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting oil was diluted with ethyl acetate (25 mL) and extracted with aqueous hydrochloric acid (1M, 25 mL), and the aqueous phase was neutralized with sodium hydroxide (s), saturated with sodium chloride and extracted with methylene chloride (3×25 mL) containing a small amount of methanol. This combined organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure, and the residue was recrystallized from ethyl acetate/hexane to give the title compound, mp 240-242° C. (dec.); MS (ESI+) for C₁₅H₁₂FN₃O₃ m/z 302 (M+H)⁺; [α]²⁵ _(D)=−25 (c 0.94, DMSO).

EXAMPLE 442 (5R)-(−)-3-[4-(4-Pyridyl)-3-fluorophenyl]-2-oxo-5-oxazolidinecarboxamide

[0709]

[0710] Following the general procedure of EXAMPLE 441, Step 5, and making non-critical variations but substituting 4-(trimethylstannyl)pyridine (U.S. Pat. No. 5,990,136, Nov. 23, 1999) for 3-(trimethylstannyl)pyridine, the title compound was obtained, mp 256-259° C. (dec.); MS (ESI+) for C₁₅H₁₂FN₃O₃ m/z 302 (M+H)⁺; [α]²⁵ _(D)=−27 (c 0.94, DMSO).

EXAMPLE 443 (5R)-(−)-3-[4-(3,6-Dihydro-2H-pyran-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinecarboxamide

[0711]

[0712] Step 1: Preparation of (5R)-3-[4-(trimethylstannyl)-3-fluorophenyl]-2-oxo-5-oxazolidinecarboxamide

[0713] A mixture of (SR)-(−)-3-[3-fluoro-4-iodophenyl]-2-oxo-5-oxazolidinecarboxamide (EXAMPLE 441, Step 3, 3.50 g, 10.0 mmol), hexamethylditin (3.44 g, 10.5 mmol) and bis(triphenylphosphine)palladium(II) chloride (140 mg, 0.200 mmol) in 1,4-dioxane (50 mL) under nitrogen was degassed, heated up to 90° C. and stirred at 90° C. for 2 hours and at ambient temperature overnight. The resulting mixture was concentrated under reduced pressure to remove dioxane, diluted with methylene chloride (75 mL), washed with saline (25 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was chromatographed on a Flash 40M 90 g silica gel (32-63 μm) cartridge, eluting with a gradient of methanol/methylene chloride (1/99-2/98), and those fractions with an R_(f)=0.26 by TLC (methanol/chloroform, 5/95) are pooled and concentrated to give the title compound, ¹H NMR (400 MHz, CDCl₃) δ 7.38 (m, 2H), 7.20 (m, 1H), 6.65 (s, 1H), 5.82 (s, 1H), 5.00 (dd, 1H), 4.26 (m, 2H), 0.35 (m, 9H).

[0714] Step 2: Preparation of (5R)-(−)-3-[4-(3,6-dihydro-2H-pyran-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidine-carboxamide

[0715] A mixture of 3,6-dihydro-2H-pyran-4-yl trifluoromethanesulfonic acid ester (U.S. Pat. No. 5,968,962, Oct. 19, 1999, 682 mg, 2.94 mmol), tris(dibenzylidene-acetone)dipalladium(0) (54 mg, 0.0588 mmol) and triphenylarsine (144 mg, 0.470 mmol) in N-methyl-2-pyrrolidinone (14.7 mL) was degassed and stirred under nitrogen for 5 minutes. (5R)-3-[4-(trimethylstannyl)-3-fluorophenyl]-2-oxo-5-oxazolidinecarboxamide (Step 1, 1.14 g, 2.94 mmol) was then added, and the resulting mixture was stirred at ambient temperature for 5 days. The reaction mixture was then diluted with water (25 mL) and extracted with ethyl acetate (3×30 mL), and the combined organic phase was washed with water (3×30 mL) and saline (20 mL), dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The crude product mixture was chromatographed on a Flash 40M 90 g silica gel (32-63 μm) cartridge, eluting with a gradient of methanol/methylene chloride (1/99-2.5/97.5), and those fractions with an R_(f)=0.40 by TLC (methanol/chloroform, 2×5/95) are pooled and concentrated to give the title compound, mp 164-169° C.; MS (ESI−) for C₁₅H₁₅N₂O₄F m/z 305 (M−H)⁻; [α]²⁵ _(D)=−23 (c 0.96, DMSO)

EXAMPLE 444 (5R)-(−)-3-[4-(Tetrahydro-2H-pyran-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinecarboxamide

[0716]

[0717] A mixture of (5R)-(−)-3-[4-(3,6-dihydro-2H-pyran-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinecarboxamide (EXAMPLE 443, Step 2, 200 mg, 0.653 mmol) and 10% palladium-on-carbon (139 mg, 0.131 mmol) in methanol (26 mL) was shaken under a 40 psi hydrogen atmosphere on a Parr apparatus for 5 hours. The catalyst was then removed by filtration through a pad of Celite, and the filtrate was concentrated under reduced pressure and chromatographed on a Flash 40S 40 g silica gel (32-63 μm) cartridge, eluting with a gradient of methanol/methylene chloride (2/98-3/97). Pooling and concentration of those fractions with an R_(f)=0.37 by TLC (methanol/chloroform, 2×5/95) gives the title compound, mp 153-156° C.; MS (ESI−) for C₁₅H₁₇N₂O₄F m/z 307 (M−H)⁻; [α]²⁵ _(D)=−21 (c 0.87, DMSO).

EXAMPLE 445 (5R)-3-[4-(3,6-Dihydro-2H-thiopyran-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinecarboxamide S-oxide

[0718]

[0719] Step 1: Preparation of (−)-methyl (5R)-3-[4-(3,6-dihydro-2H-thiopyran-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinecarboxylate

[0720] Following the general procedure of EXAMPLE 435, Step 1, and making non-critical variations but substituting isobutyl 4-(3,6-dihydro-2H-thiopyran-4-yl)-3-fluorophenylcarbamate (WO 00/44741, Aug. 3, 2000) for benzyl 3-fluoro-4-(4-morpholinyl)phenylcarbamate, the crude (5R)-3-[4-(3,6-dihydro-2H-thiopyran-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinecarboxylic acid intermediate was obtained and was used without further purification. This intermediate (540 mg crude) was taken up in methanol (16 mL), a drop of concentrated sulfuric acid was added, and the mixture was stirred at ambient temperature for 21 hours. Then, the reaction mixture was concentrated under reduced pressure and chromatographed on a Flash 40S 40 g silica gel (32-63 μm) cartridge, eluting with ethyl acetate/heptane (25/75). Pooling and concentration of those fractions with an R_(f)=0.25 by TLC (ethyl acetate/hexs, 50/50) give the title compound, mp 106-110° C.; MS (ESI+) for C₁₆H₁₆NO₄FS m/z 338 (M+H)⁺; [α]²⁵ _(D)=−36 (c 0.99, DMSO).

[0721] Step 2: Preparation of (5R)-(−)-3-[4-(3,6-dihydro-2H-thiopyran-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinecarboxamide

[0722] Following the general procedure of EXAMPLE 441, Step 3, and making non-critical variations but substituting (−)-methyl (5R)-3-[4-(3,6-dihydro-2H-thiopyran-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinecarboxylate (Step 1) for (−)-methyl (5R)-3-[3-fluoro-4-iodophenyl]-2-oxo-5-oxazolidinecarboxylate and purifying the product by recrystallization from methanol/diethyl ether, the title compound was obtained, mp 182-184° C. (dec.); MS (ESI−) for C₁₅H₁₅FN₂O₃S m/z 321 (M−H)⁻; [α]²⁵ _(D)=−24 (c 0.93, DMSO).

[0723] Step 3: Preparation of (5R)-3-[4-(3,6-dihydro-2H-thiopyran-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinecarboxamide S-oxide

[0724] A mixture of (5R)-(−)-3-[4-(3,6-dihydro-2H-thiopyran-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinecarboxamide (Step 2, 294 mg, 0.912 mmol) in methanol (18 mL) was treated with sodium periodate (205 mg, 0.958 mmol) in water (3.8 mL), and the mixture was stirred at ambient temperature for 44 hours. The resulting mixture was diluted with water (25 mL) and extracted with methylene chloride (5×30 mL), and the combined organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product mixture was triturated with acetone/diethyl ether and then filtered to give the title compound as a mixture of two diastereomers, ¹H NMR (400 MHz, DMSO-d₆) 7.87 (s, 1H), 7.63 (s, 1H), 7.52 (d, 1H), 7.39 (m, 2H), 5.83 (m, 1H), 5.04 (dd, 1H), 4.29 (t, 1H), 4.02 (dd, 1H), 3.65 (m, 1H), 3.39 (m, 1H), 3.10 (m, 1H), 2.92 (m, 2H), 2.54 (m, 1H); MS (ESI+) for C₁₅H₁₅FN₂O₄S m/z 339 (M+H)⁺.

EXAMPLE 446 (5R)-(−)-3-[4-(3,6-Dihydro-2H-thiopyran-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinecarboxamide S,S-dioxide

[0725]

[0726] A solution of (5R)-(−)-3-[4-(3,6-dihydro-2H-thiopyran-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinecarboxamide (EXAMPLE 445, Step 2, 209 mg, 0.648 mmol) in water/acetone (25/75, 13 mL) under nitrogen was treated with N-methylmorpholine N-oxide (190 mg, 1.62 mmol) and osmium tetroxide (2.5 wt % in tBuOH, 0.41 mL, 0.0324 mmol), and the mixture was stirred at ambient temperature for 43 hours. The reaction was then treated with ½-saturated aqueous sodium bisulfite (25 mL) and extracted with methylene chloride (3×25 mL), and the combined organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was chromatographed on a Flash 40S 40 g silica gel (32-63 m) cartridge, eluting with a gradient of methanol/methylene chloride (2.5/97.5-4/96), and those fractions with an R_(f)=0.48 by TLC (methanol/chloroform, 10/90) are pooled and concentrated to give the title compound, mp 206-208° C.; MS (ESI−) for C₁₅H₁₅FN₂O₅S m/z 353 (M−H)⁻; [α]²⁵ _(D)=−20 (c 0.98, DMSO).

EXAMPLE 447 (5R)-(−)-3-[4-(Tetrahydro-2H-thiopyran-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinecarboxamide S,S-dioxide

[0727]

[0728] A mixture of (5R)-(−)-3-[4-(3,6-dihydro-2H-thiopyran-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinecarboxamide S,S-dioxide (EXAMPLE 446, 73 mg, 0.206 mmol) and 10% palladium-on-carbon (44 mg, 0.0412 mmol) in methanol (21 mL) was shaken under a 40 psi hydrogen atmosphere on a Parr apparatus for 16 hours. The catalyst was then removed by filtration through a pad of Celite, rinsing with methanol and tetrahydrofuran, and the filtrate was concentrated under reduced pressure and triturated with (5% methanol/methylene chloride)/diethyl ether. Filtration then provides the title compound, mp 229-231° C. (dec.); MS (ESI−) for C₁₅H₁₇FN₂O₅S m/z 355 (M−H)⁻; [α]²⁵ _(D)=−20 (c 0.83, DMSO).

EXAMPLE 448 (5R)-(−)-3-[3-Fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinecarboxamide

[0729]

[0730] Step 1: Preparation of (−)-phenylmethyl 4-[4-[(5R)-5-(aminocarbonyl)-2-oxo-3-oxazolidinyl]-2-fluorophenyl]-1-piperazinecarboxylate

[0731] Following the general procedure of EXAMPLE 435, Step 1, and making non-critical variations but substituting benzyl 4-(4-{[benzyloxycarbonyl]amino}-2-fluorophenyl)-1-piperazinecarboxylate (J. Med. Chem. 1996, 39(3), 673-679) for benzyl 3-fluoro-4-(4-morpholinyl)phenylcarbamate, the crude 1-(phenylmethyl)-4-[4-[(5R)-5-carboxy-2-oxo-3-oxazolidinyl]-2-fluorophenyl]-1-piperazinecarboxylate intermediate was obtained [MS (ESI−) for C₂₂H₂₂N₃O₆F m/z 442 (M−H)⁻] and was used without further purification. This intermediate (1.66 g crude) was taken up in methanol (75 mL), 4 drops of concentrated sulfuric acid are added, and the mixture was stirred at ambient-temperature for 19 hours. Then, the reaction mixture was concentrated under reduced pressure and chromatographed twice on a Flash 40M 90 g silica gel (32-63 μm) cartridge, eluting with a gradient of methanol/methylene chloride (1/99-2/98). Pooling and concentration of those fractions with an R_(f)=0.64 by TLC (methanol/chloroform, 5/95) provides 740 mg of the phenylmethyl 4-[2-fluoro-4-[(5R)-5-(methoxycarbonyl)-2-oxo-3-oxazolidinyl]phenyl]-1-piperazinecarboxylate intermediate [MS (ESI+) for C₂₃H₂₄N₃O₆F m/z 458 (M+H)⁺; 75-80% purity] which was used without further purification. This intermediate was taken up in 2M ammonia in methanol (13 mL), and the resulting mixture was stirred at ambient temperature for 3 hours and then concentrated under reduced pressure. The residue was chromatographed on a Flash 40M 90 g silica gel (32-63 μm) cartridge, eluting with a gradient of methanol/methylene chloride (1/99-3/97), and those fractions with an R_(f)=0.20 by TLC (methanol/chloroform, 5/95) are pooled and concentrated to give the title compound, mp 172-175° C.; MS (ESI+) for C₂₂H₂₃N₄O₅F m/z 443 (M+H)⁺; [α]²⁵ _(D)=−17 (c 1.04, DMSO).

[0732] Step 2: Preparation of (5R)-3-[3-fluoro-4-[4-[(phenylmethoxy)acetyl]-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinecarboxamide

[0733] A mixture of (−)-phenylmethyl 4-[4-[(5R)-5-(aminocarbonyl)-2-oxo-3-oxazolidinyl]-2-fluorophenyl]-1-piperazinecarboxylate (Step 1, 415 mg, 0.938 mmol) and 10% palladium-on-carbon (100 mg, 0.0938 mmol) in methanol (45 mL) was shaken under a 45 psi hydrogen atmosphere on a Parr apparatus for 4 hours. The catalyst was then removed by filtration through a pad of Celite, and the filtrate was concentrated under reduced pressure to give 290 mg (100%) of the (5R)-3-[(3-fluoro-4-piperazinyl) phenyl]-2-oxo-5-oxazolidinecarboxamide intermediate [MS (ESI+) for C₁₄H₁₇N₄O₃F m/z 309 (M+H)⁺] which was used without further purification. A mixture of this intermediate (240 mg, 0.778 mmol) in methylene chloride (7.8 mL) under nitrogen was treated with triethylamine (163 μL, 1.17 mmol) followed by benzyloxyacetyl chloride (135 μL, 0.856 mmol), and the resulting homogeneous mixture was stirred at ambient temperature for 3 hours. The reaction mixture was then diluted with water (20 mL) and methylene chloride (20 mL), the layers are separated, and the organic phase was washed with saline (10 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the crude product which was then chromatographed on a Flash 40M 90 g silica gel (32-63 μm) cartridge, eluting with methanol/methylene chloride (2.5/97.5). Pooling and concentration of those fractions with an R_(f)=0.50 by TLC (methanol/chloroform, 10/90) provides the title compound, ¹H NMR (400 MHz, DMSO-d₆) δ 7.85 (s, 1H), 7.61 (s, 1H), 7.52 (dd, 1H), 7.36 (m, 4H), 7.31 (m, 1H), 7.24 (m, 1H), 7.06 (m, 1H), 5.01 (dd, 1H), 4.53 (s, 2H), 4.25 (m, 3H), 3.97 (dd, 1H), 3.58 (m, 4H), 2.96 (m, 4H); MS (ESI+) for C₂₃H₂₅FN₄O₅ m/z 457 (M+H)⁺.

[0734] Step 3: Preparation of (5R)-(−)-3-[3-fluoro-4-[4-(hydroxyacetyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinecarboxamide

[0735] A mixture of (5R)-3-[3-fluoro-4-[4-[(phenylmethoxy)acetyl]-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinecarboxamide (Step 2, 260 mg, 0.570 mmol) and 10% palladium-on-carbon (61 mg, 0.0570 mmol) in a mixture of methanol (5 mL) and EtOH (23 mL) was shaken under a 40 psi hydrogen atmosphere on a Parr apparatus for 22 hours. The catalyst was then removed by filtration through a pad of Celite, rinsing with tetrahydrofuran (200 mL), and the filtrate was concentrated under reduced pressure and triturated with methanol/diethyl ether. Filtration then provided the title compound, mp 232-235° C. (dec.); MS (ESI+) for C₁₆H₁₉FN₄O₅ m/z 367 (M+H)⁺; [α]²⁵ _(D)=−20 (c 0.98, DMSO).

EXAMPLE 449 (5R)-(−)-3-[4-(Thiomorpholin-4-yl)-3,5-difluorophenyl]-2-oxo-5-oxazolidinecarboxamide S,S-dioxide

[0736]

[0737] Step 1: Preparation of 4-(2,6-difluorophenyl)thiomorpholine 1,1-dioxide

[0738] Aluminum chloride (310 g, 2.3 mol) was added to chlorobenzene (2.5 L) to give a cloudy green suspension. Vinyl sulfone (230 mL, 2.3 mol) was added via funnel, followed by 2,6-difluoroaniline (250 mL, 2.3 mol). The light brown solution was heated to 110° C. Upon completion of the reaction, the heat was removed and the black solution was self-cooled to 70° C. The reaction mixture was then quenched in methylene chloride (4 L) and ice water (5 L), the aqueous phase was extracted with methylene chloride (3 L, 2 L, 2 L, 2 L) and the combined organic layers are concentrated, rediluted with branched octane (3 L), and then cooled to 0° C. for 30 minutes. The solids are filtered and washed with branched octane (2×500 mL) and are then dissolved in methylene chloride (3 L) and loaded onto a SiO₂ plug (1.8 kg). The column was eluted with dichloromethane (16 L) until clear. The methylene chloride solution was concentrated, and the solids are dissolved in hot ethyl acetate (3 L) followed by the addition of hexanes (900 mL). The black solution was self-cooled to room temperature overnight, and the resulting light amber crystal needles are filtered and washed with hexanes (4×250 mL). The solids are dried under reduced pressure at 50° C. overnight to give the title compound, ¹H NMR (CDCl₃) (δ): 7.08 (m, 1H), 6.91 (m, 2H), 3.67 (m, 4H), 3.18 (m, 4H).

[0739] Step 2: Preparation of 4-(2,6-difluoro-4-nitrophenyl)thiomorpholine 1,1-dioxide

[0740] To a suspension of 4-(2,6-difluorophenyl)thiomorpholine 1,1-dioxide (Step 1, 300 g, 1.21 mol) in 3 L of acetic acid, nitric acid (255 mL, ca. 6 mol, fuming, 90%) was added over 30 minutes at ambient temperature. A yellow precipitate forms within minutes and increases over time. The reaction was kept at room temperature for 18 hours and was then poured into 6 L of water. After stirring for 2 hours, the yellow suspension was filtered. The precipitate was washed with water (1.5 L×3) and ethanol (0.5 L×2) and dried at 50° C. overnight to give the title compound, ¹H NMR (DMSO-d₆) (δ): 8.05 (m, 2H), 3.69 (m, 4H), 3.26 (m, 4H).

[0741] Step 3: Preparation of 4-(1,1-dioxido-4-thiomorpholinyl)-3,5-difluoroaniline

[0742] To an autoclave was added 4-(2,6-difluoro-4-nitrophenyl)thiomorpholine 1,1-dioxide (Step 2, 7.0 kg, 24 moles, 1.0 eq). Raney Nickel (1.4 kg) was activated and suspended in tetrahydrofuran (4 L), and the slurry was added to the autoclave followed by additional tetrahydrofuran (66 L). The mixture was heated at 40° C. under a 40 psi hydrogen atmosphere until the reaction was complete. The mixture was then filtered, and the filtrate was directly used in the next step. A small portion of the filtrate can be concentrated and recrystallized in isopropanol to give the title compound in pure form, ¹H NMR (DMSO-d₆) (δ): 6.17 (m, 2H), 5.35 (s, 2H), 3.32 (m, 4H), 3.15 (m, 4H).

[0743] Step 4: Preparation of isobutyl 4-(1,1-dioxido-4-thiomorpholinyl)-3,5-difluorophenylcarbamate

[0744] To a 400 L glass-lined reactor containing the 4-(1,1-dioxido-4-thiomorpholinyl)-3,5-difluoroaniline/tetrahydrofuran solutions (Step 3, 12.6 kg, 48 moles, 1.0 eq) was added 47% potassium carbonate solution (14.1 kg, 48 moles, 1.0 eq). The mixture was heated to approximately 45° C., and isobutyl chloroformate (7.2 kg, 53 moles, 1.1 eq) was added while maintaining a reaction temperature between 45° C. and 55° C. The reaction was stirred at 45°-55° C. Once deemed complete, the reaction was quenched by slowly adding water (45 L) over 15 minutes. The reaction mixture was cooled to 25° C. and the phases are separated. The tetrahydrofuran solution was swapped to an isopropanol (150 L)/water (50 L) suspension, and the slurry was slowly cooled to 5° C. The yellow slurry was then filtered and the cake washed with cold isopropanol (2×30 L). The yellow solids are dried with 60° C. nitrogen to give the title compound, ¹H NMR (CDCl₃) (δ): 7.02 (m, 2H), 6.81 (s, 1H), 3.95 (d, 2H) 3.60 (m, 4H), 3.17 (m, 4H), 1.97 (m, 1H), 0.94 (d, 6H).

[0745] Step 5: Preparation of (5R)-(−)-3-[4-(thiomorpholin-4-yl)-3,5-difluorophenyl]-2-oxo-5-oxazolidinecarboxamide S,S-dioxide

[0746] Following the general procedure of EXAMPLE 448, Step 1, and making non-critical variations but substituting isobutyl 4-(1,1-dioxido-4-thiomorpholinyl)-3,5-difluorophenylcarbamate (Step 4) for benzyl 4-(4-{[benzyloxycarbonyl]amino}-2-fluorophenyl)-1-piperazinecarboxylate and purifying the final product by trituration and filtration from (10% methanol/chloroform)/diethyl ether, the title compound was obtained, mp 245-248° C. (dec.); MS (ESI+) for C₁₄H₁₅F₂N₃O₅S m/z 376 (M+H)⁺; [δ]²⁵ _(D)=−22 (c 1.00, DMSO).

EXAMPLE 450 (5R)-(−)-3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinecarboxamide—Method C

[0747]

[0748] Step 1: Preparation of ethyl (5R)-3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinecarboxylate

[0749] A solution of 3-fluoro-4-morpholinoaniline (J. Med. Chem. 1996, 39(3), 673-679, 0.796 g, 4.0 mmol), ethyl 2(R)-epoxypropanoate (0.696 g, 6.0 mmol) and lithium triflate (0.97 g, 6.2 mmol) in acetonitrile (12 mL) was stirred at 50-60° C. overnight. Solvent and excess epoxide was removed under reduced pressure, and the crude amino alcohol was redissolved in dry acetonitrile (40 mL) and 1,1′-carbonyldiimidazole (1.46 g, 9.0 mmol) was added. The mixture was stirred at ambient temperature overnight, and then the solvent was removed under reduced pressure. The residue was partitioned between ethyl acetate (70 mL) and 3% aqueous citric acid (100 mL), the layers are separated, and the organic phase was washed with 3% aqueous citric acid (3×100 mL), water and saline, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The product mixture was then purified by silica gel chromatography, eluting with ethanol/methylene chloride (2/98), and the appropriate fractions are pooled and concentrated to give the title compound, MS (ESI+) for C₁₆H₁₉N₂O₅F m/z 339 (M+H)⁺.

[0750] Step 2: Preparation of (5R)-(−)-3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinecarboxamide

[0751] A mixture of of ethyl (5R)-3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinecarboxylate (Step 1, 0.22 g, 0.65 mmol) in 2M ammonia in methanol (5-6 mL) was heated in a closed vial at 60° C. for approximately 1 hour. The resulting mixture was cooled to ambient temperature and concentrated under reduced pressure, and the crude product was recrystallized from methanol to give the title compound, MS (ESI+) for C₁₄H₁₆N₃O₄F m/z 310 (M+H)⁺.

EXAMPLE 451 (5R)-(−)-3-[3,5-Difluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinecarboxamide

[0752]

[0753] Step 1: Preparation of butyl (5R)-3-[3,5-difluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinecarboxylate

[0754] A solution of 3,5-difluoro-4-(4-morpholinyl)aniline (See U.S. Pat. No. 5,688,792, 2.00 g, 9.34 mmol), butyl 2(R)-glycidate (2.02 g, 14.0 mmol) and lithium triflate (2.18 g, 14.0 mmol) in acetonitrile (37 mL) was stirred at 60° C. under N₂ for 48 hrs. Solvent was removed under reduced pressure, and the residue was taken up in MeOH/CH₂Cl₂ (5/95, 100 mL), washed with water (2×25 mL) and saline (25 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was flushed through a Flash 40M 90 g silica gel cartridge with EtOAc/CH₂Cl₂ (10/90), and the appropriate fractions were pooled and concentrated to give the amino alcohol intermediate [R_(t)=0.10 by TLC, EtOAc/hexanes (25/75)] which was contaminated with residual starting material. This intermediate (2.5 g in two lots) was then dissolved in acetonitrile (total of 70 mL) and treated with 1,1′-carbonyldiimidazole (total of 1.69 g, 10.4 mmol, 1.5 equiv.), and the reaction mixtures were stirred at ambient temperature for 6 days and then concentrated under reduced pressure. The product mixtures were each taken up in CH₂Cl₂ (50 mL), washed with 0.1M hydrochloric acid (2×20 mL) and saline (10 mL), dried over anhydrous sodium sulfate, concentrated under reduced pressure and chromatographed on a Flash 40M 90 g silica gel cartridge with EtOAc/CH₂Cl₂ (5/95). Those fractions with an R_(f)=0.16 by TLC (EtOAc/hexanes, 25/75) were pooled and concentrated to give the title compound, mp 99-100° C.; MS (ESI+) for C₁₈H₂₂N₂O₅F₂ m/z 385 (M+H)⁺.

[0755] Step 2: Preparation of (5R)-(−)-3-[3,5-difluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinecarboxamide

[0756] The butyl (SR)-3-[3,5-difluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinecarboxylate (Step 1, 350 mg, 0.910 mmol) was treated with 7N ammonia in methanol (9.1 mL) under N₂, and the mixture was stirred at ambient temperature for 30 mins. The reaction mixture was then concentrated under reduced pressure, and the residue was recrystallized from EtOAc/hexanes to give the title compound, mp 181-183° C.; MS (ESI+) for C₁₄H₁₅N₃O₄F₂ m/z 328 (M+H)⁺; [α]²⁵ _(D) −23 (c 0.94, DMSO).

EXAMPLE 452 (5R)-(−)-3-[4-(Thiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxamide S,S-dioxide

[0757]

[0758] Step 1: Preparation of butyl (5R)-3-[4-(thiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate

[0759] A solution of 4-(4-thiomorpholinyl)aniline (See Med. Chem. Res. 1999, 9(3), 149-161, 2.60 g, 13.4 mmol), butyl 2(R)-glycidate (2.89 g, 20.1 mmol) and lithium triflate (3.13 g, 20.1 mmol) in acetonitrile (54 mL) was stirred at 60° C. under N₂ for 36 hrs. Solvent was removed under reduced pressure, and the residue was taken up in MeOH/CH₂Cl₂ (5/95, 100 mL), washed with water (50 mL) and saline (20 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was flushed through a Flash 40M 90 g silica gel cartridge with EtOAc/CH₂Cl₂ (15/85), and the appropriate fractions were pooled and concentrated to give the amino alcohol intermediate [R_(f)=0.19 by TLC, EtOAc/hexanes (25/75)] which was contaminated with the dialkylated by-product. This intermediate (4.25 g) was then dissolved in acetonitrile (125 mL) and treated with 1,1′-carbonyldiimidazole (3.05 g, 18.8 mmol, 1.5 equiv.), and the reaction mixture was stirred at ambient temperature for approximately 3 days and then concentrated under reduced pressure. The product mixture was taken up in CH₂Cl₂ (100 mL), washed with 0.1M hydrochloric acid (3×25 mL) and saline (25 mL), dried over anhydrous sodium sulfate, concentrated under reduced pressure and chromatographed on a Flash 40M 90 g silica gel cartridge with EtOAc/CH₂Cl₂ (15/85). Those fractions with an R_(f)=0.57 by TLC (EtOAc/hexanes, 50/50) were pooled and concentrated to give the title compound, mp 95.5-98° C.; MS (ESI+) for C₁₈H₂₄N₂O₄S m/z 365 (M+H)⁺.

[0760] Step 2: Preparation of butyl (5R)-3-[4-(thiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate S,S-dioxide

[0761] A solution of butyl (5R)-3-[4-(thiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate (Step 1, 600 mg, 1.65 mmol) in water/acetone (25/75, 32 mL) under N₂ was treated with N-methylmorpholine N-oxide (483 mg, 4.12 mmol) and osmium tetroxide (2.5 wt % in tBuOH, 1.03 mL, 0.0825 mmol), and the mixture was stirred at ambient temperature for 18 hrs. The reaction was then treated with ½-saturated aqueous sodium bisulfite (20 mL), diluted with water (20 mL) and extracted with CH₂Cl₂ (2×50 mL). The combined organic phase was washed with saline (20 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure, and the product mixture was chromatographed on a Flash 40S 40 g silica gel cartridge with MeOH/CH₂Cl₂ (1/99). Pooling and concentration of those fractions with an R_(f)=0.5 by TLC (MeOH/CHCl₃, 5/95) followed by recrystallization from EtOAc/hexanes gave the title compound, mp 100-102° C.; MS (ESI+) for C₁₈H₂₄N₂O₆S m/z 397 (M+H)⁺.

[0762] Step 3: Preparation of (5R)-(−)-3-[4-(thiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxamide S,S-dioxide

[0763] The butyl (5R)-3-[4-(thiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate S,S-dioxide (Step 2, 400 mg, 1.01 mmol) was treated with 7N ammonia in methanol (10.1 mL) under N₂, and the mixture was stirred at ambient temperature for 25 mins. The resulting slurry was then diluted with diethyl ether (5 mL) and filtered to give the title compound, mp 226-228° C.; MS (ESI−) for C₁₄H₁₇N₃O₅S m/z 338 (M−H)⁻; [α]²⁵ _(D) −22 (c 0.94, DMSO).

EXAMPLE 453 (5R)-(−)-3-[3-Fluoro-4-(thiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxamide S,S-dioxide

[0764]

[0765] Step 1: Preparation of butyl (5R)-3-[3-fluoro-4-(thiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate

[0766] Following the general procedure of EXAMPLE 452, Step 1, and making non-critical variations but substituting 3-fluoro-4-(4-thiomorpholinyl)aniline (See J. Med. Chem. 1996, 39(3), 680-685) for 4-(4-thiomorpholinyl)aniline, the title compound was obtained, mp 128-130° C.; MS (ESI+) for C₁₈H₂₃N₂O₄ES m/z 383 (M+H)⁺.

[0767] Step 2: Preparation of butyl (5R)-3-[3-fluoro-4-(thiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate S,S-dioxide

[0768] Following the general procedure of EXAMPLE 452, Step 2, and making non-critical variations but substituting butyl (5R)-3-[3-fluoro-4-(thiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate (Step 1) for butyl (5R)-3-[4-(thiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate, the title compound was obtained, mp 169-171° C. (dec.); MS (ESI+) for C₁₈H₂₃N₂O₆FS m/z 415 (M+H)⁺.

[0769] Step 3: Preparation of (5R)-(−)-3-[3-fluoro-4-(thiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxamide S,S-dioxide

[0770] Following the general procedure of EXAMPLE 452, Step 3, and making non-critical variations but substituting butyl (5R)-3-[3-fluoro-4-(thiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate S,S-dioxide (Step 2) for butyl (5R)-3-[4-(thiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate S,S-dioxide, the title compound was obtained, mp 245-247° C. (dec.); MS (ESI+) for C₁₄H₁₆N₃O₅FS m/z 358 (M+H)⁺; [α]²⁵ _(D) −22 (c 0.92, DMSO).

EXAMPLE 454 (5R)-(−)-3-[3-Fluoro-4-(thiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxamide S-oxide

[0771]

[0772] Step 1: Preparation of butyl (5R)-3-[3-fluoro-4-(thiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate S-oxide

[0773] A solution of sodium periodate (265 mg, 1.24 mmol) in water (5 mL) was treated with a slurry of butyl (5R)-3-[3-fluoro-4-(thiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate (EXAMPLE 20, Step 1, 450 mg, 1.18 mmol) in methanol (24 mL), and the mixture was stirred at ambient temperature for 23 hrs. The resulting mixture was diluted with water (20 mL) and saline (20 mL) and extracted with CH₂Cl₂ (2×40 mL), and the combined organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was chromatographed on a Flash 40S 40 g silica gel cartridge, eluting with a gradient of MeOH/CH₂Cl₂ (1/99-2/98), and those fractions with an R_(f)=0.37 by TLC (MeOH/CHCl₃, 5/95) were pooled and concentrated and the residue recrystallized from EtOAc/hexanes to give the title compound, mp 128-129° C.; MS (ESI+) for C₁₈H₂₃N₂O₅FS m/z 399 (M+H)⁺.

[0774] Step 2: Preparation of (5R)-(−)-3-[3-fluoro-4-(thiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxamide S-oxide

[0775] Following the general procedure of EXAMPLE 452, Step 3, and making non-critical variations, but substituting (SR)-3-[3-fluoro-4-(thiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxamide S-oxide (Step 1) for butyl (5R)-3-[4-(thiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate S,S-dioxide and purifying the product by trituration and filtration from hot acetonitrile, the title compound was obtained, mp 264-266° C. (dec.); MS (ESI+) for C₁₄H₁₆N₃O₄FS m/z 342 (M+H)⁺; [α]²⁵ _(D) −22 (c 0.39, DMSO).

EXAMPLE 455 (5R)-(−)-3-[3,5-Difluoro-4-(thiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxamide S-oxide

[0776]

[0777] Step 1: Preparation of 4-(2,6-Difluoro-4-nitrophenyl)thiomorpholine

[0778] A solution of 3,4,5-trifluoronitrobenzene (5.00 g, 28.24 mmol) in acetonitrile (60 mL) was cooled to 0° C. and treated with N,N-diisopropylethylamine (7.38 mL, 42.35 mmol) followed by thiomorpholine (2.98 mL, 29.65 mmol). The ice bath was removed and the reaction mixture stirred at room temperature under nitrogen for approximately 24 hrs, during which additional thiomorpholine (0.1 eq) was added. The solvent was removed under reduced pressure, and the residue was diluted with ethyl acetate, washed with 1N hydrochloric acid (until the washings were acidic), saturated aqueous sodium bicarbonate and saline, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give the title compound, mp 104-105° C.

[0779] Step 2: Preparation of 3,5-difluoro-4-(4-morpholinyl)aniline

[0780] A solution of 4-(2,6-difluoro-4-nitrophenyl)thiomorpholine (3.00 g, 11.5 mmol) in tetrahydrofuran (60 mL) was added to a Parr bottle containing a mixture of Raney nickel (1 g) in water (15 mL) under N₂, and the reaction mixture was shaken on a Parr apparatus under a hydrogen atmosphere at 40 psi for 24 hrs. The catalyst was removed by filtration through Celite, rinsing with tetrahydrofuran and water, the filtrate was diluted with water (50 mL) and EtOAc (50 mL), and the layers were separated. The organic phase was washed with saline (25 mL), dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and the resulting oil was chromatographed on a Flash 40M 90 g silica gel cartridge eluting with EtOAc/heptane (15/85). Pooling and concentration of those fractions with an Rt=0.19 by TLC (EtOAc/hexanes, 25/75) gave the title compound, mp 85-86° C.; MS (ESI+) for C₁₀H₁₂N₂F₂S m/z 231 (M+H)⁺.

[0781] Step 3: Preparation of butyl (5R)-3-[3,5-difluoro-4-(thiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate

[0782] Following the general procedure of EXAMPLE 452, Step 1, and making non-critical variations but substituting 3,5-difluoro-4-(4-morpholinyl)aniline (Step 2) for 4-(4-thiomorpholinyl)aniline, the title compound was obtained, mp 102-103° C.; MS (ESI+) for C₁₈H₂₂N₂O₄F₂S m/z 401 (M+H)⁺.

[0783] Step 4: Preparation of butyl (5R)-3-[3,5-difluoro-4-(thiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate S-oxide

[0784] Following the general procedure of EXAMPLE 454, Step 1, and making non-critical variations but substituting butyl (5R)-3-[3,5-difluoro-4-(thiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate (Step 3) for butyl (5R)-3-[4-(thiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate, the title compound was obtained, mp 114-116° C.; MS (ESI+) for C₁₈H₂₂N₂O₅F₂S m/z 417 (M+H)⁺.

[0785] Step 5: Preparation of (5R)-(−)-3-[3,5-Difluoro-4-(thiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxamide S-oxide

[0786] Following the general procedure of EXAMPLE 452, Step 3, and making non-critical variations, but substituting (5R)-3-[3,5-difluoro-4-(thiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxamide S-oxide (Step 4) for butyl (5R)-3-[4-(thiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate S,S-dioxide, the title compound was obtained, mp 273-276° C. (dec.); MS (ESI+) for C₁₄H₁₅N₃O₄F₂S m/z 360 (M+H)⁺; [α]²⁵ _(D) −24 (c 0.96, DMSO).

EXAMPLE 456 (SR)-3-[3-Fluoro-4-(cis-tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxamide

[0787]

[0788] Step 1: Preparation of 2-methylpropyl [3-fluoro-4-(tetrahydro-2H-thiopyran-4-yl)phenyl]carbamate

[0789] A solution of 2-methylpropyl [3-fluoro-4-(tetrahydro-4-hydroxy-2H-thiopyran-4-yl)phenyl]carbamate (See Org. Proc. Res. Dev. 2001, 5, 80-83, 4.00 g, 12.2 mmol) in trifluoroacetic acid (19 mL, 244 mmol) under N₂ was treated with triethylsilane (5.85 mL, 36.6 mmol) dropwise, stirred for 1 hr, and then added dropwise to saturated aqueous potassium carbonate (250 mL) with vigorous stirring. The mixture was extracted with diethyl ether (200 mL), and the organic phase was washed with water (2×50 mL) and saline (50 mL), dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Trituration and filtration from diethyl ether/hexanes or ethyl acetate/hexanes gave the title compound, ¹H NMR (CDCl₃, 400 MHz) δ 7.26 (m, 1H), 7.11 (t, 1H), 6.97 (m, 1H), 6.59 (bs, 1H), 3.95 (d, 2H), 2.85 (m, 3H), 2.68 (m, 2H), 2.09 (m, 2H), 1.98 (m, 1H), 1.84 (m, 2H), 0.96 (d, 6H).

[0790] Step 2: Preparation of 3-fluoro-4-(tetrahydro-2H-thiopyran-4-yl)benzenamine

[0791] A mixture of 2-methylpropyl [3-fluoro-4-(tetrahydro-2H-thiopyran-4-yl)phenyl]carbamate (Step 1, 2.12 g, 6.81 mmol) in ethylene glycol (25 mL) was treated with aqueous potassium hydroxide (45%, 25.5 g, 204 mmol) with vigorous stirring, and the mixture was heated to 95° C. and stirred at this temperature for 18 hrs. The reaction was then cooled to ambient temperature and diluted with water (50 mL) and CH₂Cl₂ (100 mL), the layers were separated, and the organic phase was washed with water (50 mL) and saline (20 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was chromatographed on a Flash 40M 90 g silica gel cartridge with a gradient of EtOAc/heptane (15/85-25/75), and those fractions with an R_(f)=0.32 by TLC (EtOAc/hexanes, 25/75) were pooled and concentrated to give the title compound, mp 96-98° C.; MS (ESI+) for C₁₁H₁₄NFS m/z 212 (M+H)⁺.

[0792] Step 3: Preparation of butyl (5R)-3-[3-fluoro-4-(tetrahydro-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate

[0793] Following the general procedure of EXAMPLE 452, Step 1, and making non-critical variations but substituting 3-fluoro-4-(tetrahydro-2H-thiopyran-4-yl)benzenamine (Step 2) for 4-(4-thiomorpholinyl)aniline, the title compound was obtained, mp 98-100° C.; MS (ESI+) for C₁₉H₂₄NO₄FS m/z 382 (M+H)⁺.

[0794] Step 4: Preparation of butyl (5R)-3-[3-fluoro-4-(cis-tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate

[0795] Following the general procedure of EXAMPLE 454, Step 1, and making non-critical variations but substituting butyl (5R)-3-[3-fluoro-4-(tetrahydro-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate (Step 3) for butyl (5R)-3-[4-(thiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate, a mixture of the cis and trans sulfoxide products in approximately a 2:1 ratio was obtained. Subsequent purification by preparative HPLC (Chiralcel OD column, EtOH eluent) followed by recrystallization from EtOAc/hexanes provided the title compound, mp 142-145° C.; MS (ESI+) for C₁₉H₂₄NO₅FS m/z 398 (M+H)⁺.

[0796] Step 5: Preparation of (5R)-3-[3-fluoro-4-(cis-tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxamide

[0797] Following the general procedure of EXAMPLE 452, Step 3, and making non-critical variations, but substituting butyl (SR)-3-[3-fluoro-4-(cis-tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate (Step 4) for butyl (5R)-3-[4-(thiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate S,S-dioxide and purifying the product by trituration and filtration from hot methanol and acetonitrile, the title compound was obtained, mp 279-281° C. (dec.); MS (ESI+) for C₁₅H₁₇N₂O₄FS m/z 341 (M+H)⁺.

EXAMPLE 457 (5R)-3-[3-Fluoro-4-(trans-tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxamide

[0798]

[0799] Step 1: Preparation of butyl (5R)-3-[3-fluoro-4-(trans-tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate

[0800] Following the general procedure of EXAMPLE 454, Step 1, and making non-critical variations but substituting butyl (5R)-3-[3-fluoro-4-(tetrahydro-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate (EXAMPLE 23, Step 3) for butyl (5R)-3-[4-(thiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate, a mixture of the cis and trans sulfoxide products in approximately a 2:1 ratio was obtained. Subsequent purification by preparative HPLC (Chiralcel OD column, EtOH eluent) followed by recrystallization from EtOAc/hexanes provided the title compound, mp 133-136° C.; MS (ESI+) for C₁₉H₂₄NO₅FS m/z 398 (M+H)⁺.

[0801] Step 2: Preparation of (5R)-3-[3-fluoro-4-(trans-tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxamide

[0802] Following the general procedure of EXAMPLE 452, Step 3, and making non-critical variations, but substituting butyl (SR)-3-[3-fluoro-4-(trans-tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate (Step 1) for butyl (5R)-3-[4-(thiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate S,S-dioxide, the title compound was obtained, mp 201-203° C.; MS (ESI+) for C₁₅H₁₇N₂O₄FS m/z 341 (M+H)⁺.

EXAMPLE 458 (5R)-(−)-3-[4-(tetrahydro-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxamide S,S-dioxide

[0803]

[0804] Step 1: Preparation of 2-methylpropyl 4-bromophenylcarbamate

[0805] A solution of 4-bromoaniline (10.0 g, 58.1 mmol) in tetrahydrofuran (230 mL) was treated with sodium bicarbonate (9.77 g, 116.2 mmol) and water (100 mL) followed by isobutyl chloroformate (8.3 mL, 63.9 mmol), and the mixture was stirred at ambient temperature for 2 hrs. The mixture was then diluted with water (100 mL) and EtOAc (100 mL), the layers were separated, and the organic phase was washed with water (50 mL) and saline (50 mL), dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Recrystallization of the resulting solid from EtOAc/hexanes provided the title compound, mp 95-96° C.; MS (ESI−) for C₁₁H₁₄NO₂Br m/z 270 (M−H)⁻.

[0806] Step 2: Preparation of 2-methylpropyl [4-(tetrahydro-4-hydroxy-2H-thiopyran-4-yl)phenyl]carbamate

[0807] A solution of 2-methylpropyl 4-bromophenylcarbamate (Step 1, 10.0 g, 36.7 mmol) in anhydrous tetrahydrofuran (184 mL) at −78° C. under N₂ was treated n-butyllithium (1.6M in hexanes, 48.2 mL, 77.1 mmol) dropwise over 20 mins, and the mixture was stirred at −78° C. for 45 mins. The resulting slurry was then treated with a solution of tetrahydro-2H-thiopyran-4-one (4.48 g, 38.5 mmol) in anhydrous tetrahydrofuran (38 mL) dropwise over 5 mins to give an opaque mixture which was allowed to slowly warm to 0° C. with stirring over approximately 2.5 hrs. The mixture was then quenched by the slow addition of saturated aqueous ammonium chloride (75 mL), water (75 mL) was added, and the layers were separated. The organic phase was washed with water (50 mL) and saline (50 mL), dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and the crude product was recrystallized from EtOAc/hexanes to give the title compound, mp 150-151° C.; MS (ESI−) for C₁₆H₂₃NO₃S m/z 308 (M−H)⁻.

[0808] Step 3: Preparation of 2-methylpropyl [4-(tetrahydro-2H-thiopyran-4-yl)phenyl]carbamate

[0809] Following the general procedure of EXAMPLE 456, Step 1, and making non-critical variations but substituting 2-methylpropyl [4-(tetrahydro-4-hydroxy-2H-thiopyran-4-yl)phenyl]carbamate (Step 2) for 2-methylpropyl [3-fluoro-4-(tetrahydro-4-hydroxy-2H-thiopyran-4-yl)phenyl]carbamate and purifying the product by recrystallization from EtOAc/hexanes, the title compound was obtained, mp 126-128° C.; MS (ESI−) for C₁₆H₂₃NO₂S m/z 292 (M−H)⁻.

[0810] Step 4: Preparation of 4-(tetrahydro-2H-thiopyran-4-yl)benzenamine

[0811] Following the general procedure of EXAMPLE 456, Step 2, and making non-critical variations but substituting 2-methylpropyl [4-(tetrahydro-2H-thiopyran-4-yl)phenyl]carbamate (Step 3) for 2-methylpropyl [3-fluoro-4-(tetrahydro-2H-thiopyran-4-yl)phenyl]carbamate, the title compound was obtained, mp 103-106° C.; MS (ESI+) for C₁₁H₁₅NS m/z 194 (M+H)⁺.

[0812] Step 5: Preparation of butyl (5R)-3-[4-(tetrahydro-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate

[0813] Following the general procedure of EXAMPLE 452, Step 1, and making non-critical variations but substituting 4-(tetrahydro-2H-thiopyran-4-yl)benzenamine (Step 4) for 4-(4-thiomorpholinyl)aniline, the title compound was obtained, mp 94-96° C.; MS (ESI+) for C₁₉H₂₅NO₄s m/z 364 (M+H)⁺.

[0814] Step 6: Preparation of butyl (SR)-3-[4-(tetrahydro-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate S,S-dioxide

[0815] Following the general procedure of EXAMPLE 452, Step 2, and making non-critical variations but substituting butyl (5R)-3-[4-(tetrahydro-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate (Step 5) for butyl (5R)-3-[4-(thiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate, the title compound was obtained, mp 176-179° C.; MS (ESI+) for C₁₉H₂₅NO₆S m/z 396 (M+H)⁺.

[0816] Step 7: Preparation of (5R)-(−)-3-[4-(tetrahydro-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxamide S,S-dioxide

[0817] Following the general procedure of EXAMPLE 452, Step 3, and making non-critical variations, but substituting butyl (5R)-3-[4-(tetrahydro-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate S,S-dioxide (Step 6) for butyl (5R)-3-[4-(thiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate S,S-dioxide, the title compound was obtained, mp 211-212° C.; MS (ESI−) for C₁₅H₁₈N₂O₅S m/z 337 (M−H)⁻; [□]²⁵ _(D) −19 (c 0.95, DMSO)

EXAMPLE 459 (5R)-3-[4-(cis-tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-S-oxazolidinecarboxamide

[0818]

[0819] Step 1: Preparation of butyl (5R)-3-[4-(cis-tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate

[0820] Following the general procedure of EXAMPLE 459, Step 1, and making non-critical variations but substituting butyl (SR)-3-[4-(tetrahydro-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate (EXAMPLE 458, Step 5) for butyl (5R)-3-[4-(thiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate, a mixture of the cis and trans sulfoxide products in approximately a 2:1 ratio was obtained. Subsequent purification by preparative HPLC (Chiralcel OD column, EtOH eluent) followed by recrystallization from EtOAc/hexanes provided the title compound, mp 127-130° C.; MS (ESI+) for C₁₉H₂₅NO₅S m/z 380 (M+H)⁺.

[0821] Step 2: Preparation of (5R)-3-[4-(cis-tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxamide

[0822] Following the general procedure of EXAMPLE 452, Step 3, and making non-critical variations, but substituting butyl (5R)-3-[4-(cis-tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate (Step 1) for butyl (5R)-3-[4-(thiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate S,S-dioxide, the title compound was obtained, mp 269-273° C. (dec.); MS (ESI−) for C₁₅H₁₈N₂O₄S m/z 321 (M−H)-.

EXAMPLE 460 (SR)-3-[4-(trans-tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxamide

[0823]

[0824] Step 1: Preparation of butyl (5R)-3-[4-(trans-tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate

[0825] Following the general procedure of EXAMPLE 454, Step 1, and making non-critical variations but substituting butyl (SR)-3-[4-(tetrahydro-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate (EXAMPLE 458, Step 5) for butyl (5R)-3-[4-(thiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate, a mixture of the cis and trans sulfoxide products in approximately a 2:1 ratio was obtained. Subsequent purification by preparative HPLC (Chiralcel OD column, EtOH eluent) followed by recrystallization from EtOAc/hexanes provided the title compound, mp 115-117° C.; MS (ESI+) for C₁₉H₂₅NO₅S m/z 380 (M+H)⁺.

[0826] Step 2: Preparation of (5R)-3-[4-(trans-tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxamide

[0827] Following the general procedure of EXAMPLE 452, Step 3, and making non-critical variations, but substituting butyl (5R)-3-[4-(trans-tetrahydro-1-oxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate (Step 1) for butyl (5R)-3-[4-(thiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate S,S-dioxide, the title compound was obtained, mp 174-175° C.; MS (ESI−) for C₁₅H₁₈N₂O₄S m/z 321 (M−H)⁻.

EXAMPLE 461 (5R)-3-[4-(Tetrahydro-2H-thiopyran-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinecarboxamide S,S-dioxide—Method B

[0828]

[0829] Step 1: Preparation of 2-methylpropyl [4-(tetrahydro-1,1-dioxido-2H-thiopyran-4-yl)-3-fluorophenyl]carbamate

[0830] Following the general procedure of EXAMPLE 452, Step 2, and making non-critical variations but substituting 2-methylpropyl [4-(tetrahydro-2H-thiopyran-4-yl)-3-fluorophenyl]carbamate (EXAMPLE 456, Step 1) for butyl (5R)-3-[4-(thiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate, the title compound is obtained, ¹H NMR (CDCl₃) (δ) 7.36 (bd, 1H), 7.14 (t, 1H), 6.99 (m, 1H), 6.70 (bs, 1H), 3.95 (d, 2H), 3.14 (m, 4H), 3.07 (m, 1H), 2.38 (m, 2H), 2.18 (m, 2H), 1.95 (m,1H), 0.96 (d, 6H).

[0831] Step 2: Preparation of (5R)-3-[4-(tetrahydro-2H-thiopyran-4-yl)-3-fluorophenyl]-5-hydroxymethyl-2-oxazolidinone S,S-dioxide

[0832] A solution of 2-methylpropyl [4-(tetrahydro-1,1-dioxido-2H-thiopyran-4-yl)-3-fluorophenyl]carbamate (Step 1, 2.00 g, 5.82 mmol) in dry tetrahydrofuran at −78° C. under N₂ was treated with n-butyllithium (1.6M in hexanes, 3.82 mL, 6.11 mmol) dropwise and stirred at 78° C. for 45 mins. Then, (R)-glycidyl butyrate (0.86 mL, 6.11 mmol) was added dropwise, and the resulting mixture was stirred at −78° C. for 30 mins and at ambient temperature for 2.75 days. The reaction mixture was then quenched with saturated aqueous ammonium chloride (15 mL), diluted with water (15 mL) and EtOAc (25 mL), and the layers were separated. The organic phase was diluted with small amounts of methylene chloride, methanol and tetrahydrofuran in an attempt to dissolve a precipitate that had formed and was then washed with water (20 mL) and saline (20 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting solid was then diluted with hot methanol/EtOAc (1:5, 100 mL), followed by hexanes (150 mL), and filtered to give the title compound, ¹H NMR (DMSO) (δ) 7.51 (dd, 1H), 7.37 (t, 1H), 7.30 (m, 1H), 5.21 (t, 1H), 4.70 (m, 1H), 4.07 (t, 1H), 3.81 (dd, 1H), 3.65 (m, 1H), 3.55 (m, 1H), 3.37 (m, 2H), 3.20 (m, 1H), 3.10 (m, 2H), 2.15 (m, 2H), 2.03 (m, 2H).

[0833] Step 3: Preparation of methyl (5R)-3-[4-(tetrahydro-2H-thiopyran-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinecarboxylate S,S-dioxide

[0834] A mixture of ruthenium(III) trichloride (29 mg, 0.139 mmol, 4 mol %), sodium periodate (3.21 g, 15.0 mmol), and sodium dihydrogen phosphate monohydrate (2.60 g, 18.8 mmol) in water/methylene chloride (10:1, 21 mL) was treated with a suspension of (5R)-3-[4-(tetrahydro-2H-thiopyran-4-yl)-3-fluorophenyl]-5-hydroxymethyl-2-oxazolidinone S,S-dioxide (Step 2, 1.20 g, 3.49 mmol) in acetonitrile (35 mL), and the resulting mixture was stirred at ambient temperature for 24 hrs and was then adjusted to pH 2 with aqueous hydrochloric acid (1M) and extracted with methylene chloride (3×100 mL). The combined organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure, and the residue was flushed through a Flash 40M 90 g silica gel cartridge with a gradient of CH₃CN/CH₂Cl₂ (20/80-40/60) containing 1% formic acid. Those fractions containing the carboxylic acid intermediate (920 mg total) were pooled and concentrated, and the white solid was dissolved in methanol (25 mL) and treated with 3 to 4 drops of concentrated sulfuric acid. The resulting mixture was stirred at ambient temperature for 4 hrs and was then concentrated under reduced pressure and chromatographed on a Flash 40S 40 g silica gel cartridge, eluting with a gradient of MeOH/CH₂Cl₂ (1/99-2/98). Pooling and concentration of those fractions with an R_(f)=0.53 by TLC (MeOH/CH₂Cl₂, 5/95) provided the title compound as an amorphous solid, ¹H NMR (CDCl₃) (δ) 7.50 (dd, 1H), 7.25 (t, 1H), 7.15 (m, 1H), 5.09 (dd, 1H), 4.27 (t, 1H), 4.13 (dd, 1H), 3.88 (s, 3H), 3.15 (m, 4H), 3.11 (m, 1H), 2.40 (m, 2H), 2.19 (m, 2H).

[0835] Step 4: Preparation of (SR)-3-[4-(tetrahydro-2H-thiopyran-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinecarboxamide S,S-dioxide

[0836] Following the general procedure of EXAMPLE 452, Step 3, and making non-critical variations but substituting methyl (5R)-3-[4-(tetrahydro-2H-thiopyran-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinecarboxylate S,S-dioxide (Step 3) for butyl (5R)-3-[4-(thiomorpholin-4-yl)phenyl]-2-oxo-5-oxazolidinecarboxylate S,S-dioxide and purifying the product by trituration and filtration from (5% MeOH/CH₂Cl₂)/Et₂O, the title compound was obtained, mp 231-234° C. (dec.); MS (ESI−) for C₁₅H₁₇FN₂O₅S m/z 355 (M−H)⁻.

[0837] Additional Examples of amide-containing compounds that can be used in the present invention are disclosed below.

EXAMPLE 462 N-{3-[3-fluoro-4-(5-oxo-5,6-dihydro-4H-[1,3,4]thiadiazin-2-yl)-phenyl]-2-oxo-oxazolidin-5(S)-ylmethyl}-acetamide EXAMPLE 463 N-{3-[3-fluoro-4-(6(S)-methyl-5-oxo-5,6-dihydro-4H-[1,3,4]thiadiazin-2-yl)-phenyl]-2-oxo-oxazolidin-5(S)-ylmethyl}-acetamide EXAMPLE 464 N-{3-[3-fluoro-4-(6(R)-methyl-5-oxo-5,6-dihydro-4H-[1,3,4]thiadiazin-2-yl)-phenyl]-2-oxo-oxazolidin-5(S)-ylmethyl}-acetamide EXAMPLE 465 N-{3-[3-fluoro-4-(5-oxo-5,6-dihydro-4H-[1,3,4]thiadiazin-2-yl)-phenyl]-2-oxo-oxazolidin-5 (S)-ylmethyl}-propionamide EXAMPLE 466 cyclopropanecarboxylic acid {3-[3-fluoro-4-(5-oxo-5,6-dihydro-4H-[1,3,4]thiadiazin-2-yl)-phenyl]-2-oxo-oxazolidin-5(S)-ylmethyl}-amide EXAMPLE 467 N-{3-[3-fluoro-4-(5-oxo-5,6-dihydro-4H-[1,3,4]thiadiazin-2-yl)-phenyl]-2-oxo-oxazolidin-5 (S)-ylmethyl}-thioacetamide EXAMPLE 468 N-{3-[3-fluoro-4-(5-thioxo-5,6-dihydro-4H-[1,3,4]thiadiazin-2-yl)-phenyl]-2-oxo-oxazolidin-5 (S)-ylmethyl}-thioacetamide EXAMPLE 469 N-{3-[3-fluoro-4-(5-oxo-5,6-dihydro-4H-[1,3,4]thiadiazin-2-yl)-phenyl]-2-oxo-oxazolidin-5 (S)-ylmethyl}-acetamide EXAMPLE 470 N-{3-[3-fluoro-4-(5-oxo-5,6-dihydro-4H-[1,3,4]thiadiazin-2-yl)-phenyl]-2-oxo-oxazolidin-5-ylmethyl}-3-(4-hydroxy-phenyl)-acrylamide EXAMPLE 471 N-{3-[4-(6,6-dimethyl-5-oxo-5,6-dihydro-4H-[1,3,4]thiadiazin-2-yl)-3-fluoro-phenyl]-2-oxo-oxazolidin-5(S)-ylmethyl}-acetamide EXAMPLE 472 N-{3-[3-fluoro-4-(6-ethyl-5-oxo-5,6-dihydro-4H-[1,3,4]thiadiazin-2-yl)-phenyl]-2-oxo-oxazolidin-5(S)-ylmethyl}-acetamide EXAMPLE 473 N-{3-[3-fluoro-4-(9-oxo-5-thia-7,8-diaza-spiro[3.5]non-6-en-6-yl)-phenyl]-2-oxo-oxazolidin-5(S)-ylmethyl}-acetamide EXAMPLE 474 N-{3-[3-fluoro-4-(5-oxo-6-phenyl-5,6-dihydro-4H-[1,3,4]thiadiazin-2-yl)-phenyl]-2-oxo-oxazolidin-5(S)-ylmethyl}-acetamide EXAMPLE 475 N-{3-[3-fluoro-4-(5-oxo-5,6-dihydro-4H-[1,3,4]thiadiazin-2-yl)-phenyl]-2-oxo-oxazolidin-5(S)-ylmethyl}-2-hydroxy-acetamide EXAMPLE 476 N-{3-[3-fluoro-4-(5-oxo-5,6-dihydro-4H-[1,3,4]thiadiazin-2-yl)-phenyl]-2-oxo-oxazolidin-5(S)-ylmethyl}-3-oxo-butyramide EXAMPLE 477 N-{3-[3-fluoro-4-(5-oxo-5,6-dihydro-4H-[1,3,4]thiadiazin-2-yl)-phenyl]-2-oxo-oxazolidin-5(S)-ylmethyl}-3-(4-fluoro-phenyl)-3-oxo-propionamide, EXAMPLE 478 N-{3-[3-fluoro-4-(5-oxo-5,6-dihydro-4H-[1,3,4]thiadiazin-2-yl)-phenyl]-2-oxo-oxazolidin-5(S)-ylmethyl}-3-[4-(hydroxyimino-methyl)-phenyl]-acrylamide EXAMPLE 479 N-{3-[3-fluoro-4-(5-oxo-5,6-dihydro-4H-[1,3,4]thiadiazin-2-yl)-phenyl]-2-oxo-oxazolidin-5(S)-ylmethyl}-3-[4-(methoxyimino-methyl)-phenyl]-acrylamide EXAMPLE 480 N-{3-[4-(6,6-dimethyl-1,1,5-trioxo-1,4,5,6-tetrahydro-1^(δ6)-[1,3,4]thiadiazin-2-yl)-3-fluoro-phenyl]-2-oxo-oxazolidin-5(S)-ylmethyl}-acetamide EXAMPLE 481 N-{3-[3-fluoro-4-(4-methyl-5-oxo-5,6-dihydro-4H-[1,3,4]thiadiazin-2-yl)-phenyl]-2-oxo-oxazolidin-5(S)-ylmethyl}-acetamide EXAMPLE 482 N-{3-[3-fluoro-4-(5-oxo-6-propyl-5,6-dihydro-4H-[1,3,4]thiadiazin-2-yl)-phenyl]-2-oxo-oxazolidin-5(S)-ylmethyl}-acetamide EXAMPLE 483 N-{3-[3-fluoro-4-(6-isopropyl-5-oxo-5,6-dihydro-4H-[1,3,4]thiadiazin-2-yl)-phenyl]-2-oxo-oxazolidin-5(S)-ylmethyl}-acetamide EXAMPLE 484 N-{3-[3-fluoro-4-(6-fluoro-5-oxo-5,6-dihydro-4H-[1,3,4]thiadiazin-2-yl)-phenyl]-2-oxo-oxazolidin-5(S)-ylmethyl}-acetamide EXAMPLE 485 N-{3-[3-fluoro-4-(6-hydroxymethyl-5-oxo-5,6-dihydro-4H-[1,3,4]thiadiazin-2-yl)-phenyl]-2-oxo-oxazolidin-5(S)-ylmethyl}-acetamide EXAMPLE 486 N-{3-[3-fluoro-4-(6-(2-hydroxy-ethyl)-5-oxo-5,6-dihydro-4H-[1,3,4]thiadiazin-2-yl)-phenyl]-2-oxo-oxazolidin-5(S)-ylmethyl}-acetamide EXAMPLE 487 N-(3-{3-fluoro-4-(6-(4-hydroxy-phenyl)-5-oxo-5,6-dihydro-4H-[1,3,4]thiadiazin-2-yl]-phenyl}-2-oxo-oxazolidin-5(S)-ylmethyl)-acetamide EXAMPLE 488 N-{3-[4-(6,6-dimethyl-1,5-dioxo-1,4,5,6-tetrahydro-1^(δ4)-[1,3,4]-thiadiazin-2-yl)-3-fluoro-phenyl]-2-oxo-oxazolidin-5(S)-ylmethyl}-acetamide EXAMPLE 489 N-[[(5S)-3-[4-(3,4-dihydro-2H-thiopyran-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]-2,2,2-trifluoroacetamide EXAMPLE 490 N-[[(5S)-3-[4-(3,4-dihydro-2H-thiopyran-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide EXAMPLE 491 N-[[(5S)-3-[4-(3,4-dihydro-2H-thiopyran-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]ethanethioamide EXAMPLE 492 N-[[(5S)-3-[4-(3,4-dihydro-1-oxido-2H-thiopyran-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide EXAMPLE 493 N-[[(5S)-3-[4-(3,4-dihydro-1,1-dioxido-2H-thiopyran-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide EXAMPLE 494 N-[[(5S)-3-[4-(3,4-dihydro-1-oxido-2H-thiopyran-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]ethanethioamide, EXAMPLE 495 N-[[(5S)-3-[4-(2,3-dihydro-1,1-dioxido-4H-1,4-thiazin-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide EXAMPLE 496 N-[[(5S)-3-[4-(2,3-dihydro-1,1-dioxido-4H-1,4-thiazin-4-yl)-3,5-difluorophenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide EXAMPLE 497 N-[[(5S)-3-[4-(3,4-dihydro-1,1-dioxido-2H-thiopyran-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]-2,2-difluoroacetamide EXAMPLE 498 N-[[(5S)-3-[4-(3,4-dihydro-1,1-dioxido-2H-thiopyran-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]-2,2-difluoroethanethioamide EXAMPLE 499 2,2-Dichloro-N-[[(5S)-3-[4-(3,4-dihydro-1,1-dioxido-2H-thiopyran-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide EXAMPLE 500 N-[[(5S)-3-[4-(3,4-dihydro-4-hydroxy-1,1-dioxido-2H-thiopyran-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide EXAMPLE 501 N-[[(5S)-3-[3-Fluoro-4-(4-fluoro-3,4-dihydro-1,1-dioxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide EXAMPLE 502 N-[[(5S)-3-[4-(3,4-dihydro-1,1-dioxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide EXAMPLE 503 AT-[[(5S)-3-[4-(3,4-dihydro-1,1-dioxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2,2-difluoroacetamide, EXAMPLE 504 2,2-dichloro-N-[[(5S)-3-[4-(3,4-dihydro-1,1-dioxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide EXAMPLE 505 [[(5S)-3-[4-(3,4-dihydro-1,1-dioxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2,2-difluoroethanethioamide EXAMPLE 506 N-[[(5S)-3-[4-(3,4-dihydro-1,1-dioxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]propionamide EXAMPLE 507 N-[[(5S)-3-[4-(3,4-dihydro-1,1-dioxido-2H-thiopyran-4-yl)-3,5-difluorophenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide EXAMPLE 508 N-[[(5S)-3-[4-(2,3-dihydro-1,1-dioxido-4H-1,4-thiazin-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]-2,2-difluoroethanethioamide EXAMPLE 509 2,2-dichloro-N-[[(5S)-3-[4-(2,3-dihydro-1,1-dioxido-4H-1,4-thiazin-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide EXAMPLE 510 N-[[(5S)-3-[4-(2,3-dihydro-1,1-dioxido-4H-1,4-thiazin-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]-2,2-difluoroacetamide EXAMPLE 511 N-[[(5S)-3-[4-(2,3-dihydro-1,1-dioxido-4H-1,4-thiazin-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2,2-difluoroethanethioamide EXAMPLE 512 2,2-dichloro-N-[[(5S)-3-[4-(2,3-dihydro-1,1-dioxido-4H-1,4-thiazin-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide EXAMPLE 513 N-[[(5S)-3-[4-(2,3-dihydro-111-dioxido-4H-1,4-thiazin-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2,2-difluoroacetamide EXAMPLE 514 N-[[(5S)-3-[4-(2,3-Dihydro-1,1-dioxido-4H-1,4-thiazin-4-yl)-3,5-difluorophenyl]-2-oxo-5-oxazolidinyl]methyl]-2,2-difluoroethanethioamide EXAMPLE 515 2,2-dichloro-N-[[(5S)-3-[4-(2,3-dihydro-1,1-dioxido-4H-1,4-thiazin-4-yl)-3,5-difluorophenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide, or EXAMPLE 516 N-[[(5S)-3-[4-(2,3-dihydro-1,1-dioxido-4H-1,4-thiazin-4-yl)-3,5-difluorophenyl]-2-oxo-5-oxazolidinyl]methyl]-2,2-difluoroacetamide EXAMPLE 517 N-[[(5S)-3-[4-(2,3-dihydro-1,1-dioxido-4H-1,4-thiazin-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide EXAMPLE 518 2,2-dichloro-N-[[(5S)-3-[4-(3,4-dihydro-1,1-dioxido-2H-thiopyran-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide EXAMPLE 519 2,2-dichloro-N-[[(5S)-3-[4-(3,4-dihydro-1,1-dioxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide EXAMPLE 520 2,2-dichloro-N-[[(5S)-3-[4-(2,3-dihydro-1,1-dioxido-4H-1,4-thiazin-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide EXAMPLE 521 2,2-dichloro-N-[[(5S)-3-[4-(2,3-dihydro-1,1-dioxido-4H-1,4-thiazin-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide EXAMPLE 522 N-[[(5S)-3-[4-(2,3-dihydro-1,1-dioxido-4H-1,4-thiazin-4-yl)-3,5-difluorophenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide EXAMPLE 523 N-[[(5S)-3-[4-(3,4-dihydro-1,1-dioxido-2H-thiopyran-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]-2,2-difluoroacetamide EXAMPLE 524 N-[[(5S)-3-[4-(3,4-dihydro-1,1-dioxido-2H-thiopyran-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]-2,2-difluoroethanethioamide EXAMPLE 525 N-[[(5S)-3-[4-(3,4-dihydro-1,1-dioxido-2H-thiopyran-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2,2-difluoroacetamide EXAMPLE 526 N-[[(5S)-3-[4-(2,3-dihydro-1,1-dioxido-4H-1,4-thiazin-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]-2,2-difluoroethanethioamide EXAMPLE 527 N-[[(5S)-3-[4-(2,3-dihydro-1,1-dioxido-4H-1,4-thiazin-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]-2,2-difluoroacetamide EXAMPLE 528 N-[[(5S)-3-[4-(2,3-dihydro-1,1-dioxido-4H-1,4-thiazin-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-2,2-difluoroethanethioamide, or EXAMPLE 529 2,2-dichloro-N-[[(5S)-3-[4-(2,3-dihydro-1,1-dioxido-4H-1,4-thiazin-4-yl)-3,5-difluorophenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide, EXAMPLE 530 (S)-N-[[3-[3-fluoro-4-(1,2,3,4,6,7-hexahydro-5-oxo-1,4-diazepin-1-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide EXAMPLE 531 (S)-N-[[3-[3-fluoro-4-(1,2,3,4,6,7-hexahydro-5-oxo-1,4-diazepin-1-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide EXAMPLE 532 (S)-N-[[3-[3-fluoro-4-(1,2,3,4,6,7-hexahydro-4-methyl-5-oxo-1,4-diazepin-1-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide, or EXAMPLE 533 (S)-N-[[3-[3-fluoro-4-(1,2,3,4,6,7-hexahydro-4-methyl-5-oxo-1,4-diazepin-1-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]thioacetamide EXAMPLE 534 N-[[(5S)-3-[3-fluoro-4-[tetrahydro-1,1-dioxido-2-(2-propenyl)-2H-1,2-thiazin-4-yl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide EXAMPLE 535 N-[[(5S)-3-[3-fluoro-4-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide EXAMPLE 536 N-[[(5S)-3-[3-fluoro-4-(tetrahydro-1,1-dioxido-2H-1,2-thiazin-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]ethanethioamide EXAMPLE 537 N-[[(5S)-3-[-fluoro-4-(tetrahydro-2-methyl-1,1-dioxido-2H-1,2-thiazin-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]ethanethioamide EXAMPLE 538 N-[[(5S)-3-[4-(2,2-dioxido-1,2-oxathian-5-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]ethanethioamide, EXAMPLE 539 N-[[(5S)-3-[4-(1,1-dioxido-4-isothiazolidinyl)-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]ethanethioamide, or EXAMPLE 540 N-[[(5S)-3-[3-fluoro-4-(tetrahydro-2-methyl-1,1-dioxido-2H-1,2-thiazin-4-yl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide EXAMPLE 541 N-({(5S)-3-[(2R)-1-(2-fluoroethyl)-2-methyl-2,3-dihydro-1H-indol-5-yl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide EXAMPLE 542 N-{[(5S)-3-((2R)-1-glycoloyl-2-methyl-2,3-dihydro-1H-indol-5-yl)-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide EXAMPLE 543 N-({(5S)-3-[(2R)-1-glycoloyl-2-methyl-2,3-dihydro-1H-indol-5-yl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide EXAMPLE 544 N-({(5S)-3-[(2R)-1-formyl-2-methyl-2,3-dihydro-1H-indol-5-yl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide EXAMPLE 545 N-({(5S)-3-[(2R)-1-formyl-2-methyl-2,3-dihydro-1H-indol-5-yl]-2-oxo-1,3-oxazolidin-5-yl}methyl)propanamide EXAMPLE 546 N-({(5S)-3-[(2R)-1-formyl-2-methyl-2,3-dihydro-1H-indol-5-yl]-2-oxo-1,3-oxazolidin-5-yl}methyl)ethanethioamide EXAMPLE 547 N-({(5S)-3-[(2R)-1-(2-methoxyacetyl)-2-methyl-2,3-dihydro-1H-indol-5-yl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide EXAMPLE 548 N-({(5S)-3-[(2R)-1-acetyl-2-methyl-2,3-dihydro-1H-indol-5-yl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide EXAMPLE 549 N-[((5S)-3-{(2R)-2-methyl-1-[(methylamino)carbothioyl]-2,3-dihydro-1H-indol-5-yl}-2-oxo-1,3-oxazolidin-5-yl)methyl]acetamide EXAMPLE 550 N-({(5S)-3-[(2R)-1-glycoloyl-2-methyl-2,3-dihydro-1H-indol-5-yl]-2-oxo-1,3-oxazolidin-5-yl}methyl)ethanethioamide EXAMPLE 551 N-{[(5S)-3-[(2R)-1-formyl-2-methyl-1,2,3,4-tetrahydro-6-quinolinyl]-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide EXAMPLE 552 N-{[(5S)-3-[(2R)-1-glycoloyl-2-methyl-1,2,3,4-tetrahydro-6-quinolinyl]-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide EXAMPLE 553 N-({(5S)-3-[(2R)-1-formyl-2-methyl-1,2,3,4-tetrahydro-6-quinolinyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide EXAMPLE 554 N-({(5S)-3-[(2R)-1-formyl-2-methyl-1,2,3,4-tetrahydro-6-quinolinyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)ethanethioamide EXAMPLE 555 N-{[(5S)-3-[(3R)₄-Formyl-3-methyl-3,4-dihydro-2H-1,4-benzoxazin-7-yl]-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide EXAMPLE 556 N-({(5S)-3-[(3R)-4-Formyl-3-methyl-3,4-dihydro-2H-1,4-benzoxazin-7-yl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide EXAMPLE 557 N-({(5S)-3-[(3R)-4-Formyl-3-methyl-3,4-dihydro-2H-1,4-benzoxazin-7-yl]-2-oxo-1,3-oxazolidin-5-yl}methyl)ethanethioamide EXAMPLE 558 N-({(5S)-3-[(2R)₂-(fluoromethyl)-1-formyl-2,3-dihydro-1H-indol-5-yl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide EXAMPLE 559 N-{[(5R)-3-(2(+)-methyl-2,3-dihydro-1-benzothien-5-yl)-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide, or EXAMPLE 560 N-[[(5S)-3-[2-(1,1-dimethylethyl)-1-formyl-2,3-dihydro-1H-indol-5-yl]-2-oxo-5-oxazolidinyl]methyl]ethanethioamide EXAMPLE 561 N-{[(5S)-3-(1-Methyl-2,2-dioxo-2,3-dihydro-1H-2,1-benzisothiazol-5-yl)-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide EXAMPLE 562 N-({(5S)-3-[1-(2-Fluoroethyl)-2,2-dioxo-2,3-dihydro-1H-2,1-benzisothiazol-5-yl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide EXAMPLE 563 N-({(5S)-3-[1-(2-Nitriloethyl)-2,2-dioxo-2,3-dihydro-1H-2,1-benzisothiazol-5-yl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide EXAMPLE 564 N-({(5S)-3-[1-(2-Methoxyethyl)-2,2-dioxo-2,3-dihydro-1H-2,1-benzisothiazol-5-yl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide, or EXAMPLE 565 N-({(5S)-3-[1-(2-Fluoroethyl)-2,2-dioxo-2,3-dihydro-1H-2,1-benzisothiazol-5-yl]-2-oxo-1,3-oxazolidin-5-yl}methyl)ethanethioamide EXAMPLE 566 (−)-N-[[(5S)-3-[2-formyl-1,2,3,4-tetrahydro-6-isoquinolinyl]-2-oxo-5-oxazolidinyl]methyl]acetamide EXAMPLE 567 (−)-N-[[(5S)-3-[2-[(acetyloxy)acetyl]-1,2,3,4-tetrahydro-6-isoquinolinyl]-2-oxo-5-oxazolidinyl]methyl]acetamide EXAMPLE 568 (−)-N-[[(5S)-3-[2-[(hydroxy)acetyl]-1,2,3,4-tetrahydro-6-isoquinolinyl]-2-oxo-5-oxazolidinyl]methyl]acetamide EXAMPLE 569 (+)-N-[[(5S)-3-[2-formyl-1,2,3,4-tetrahydro-6-isoquinolinyl]-2-oxo-5-oxazolidinyl]methyl]ethanethioamide, or EXAMPLE 570 (+)-N-[[(5S)-3-[2-[(hydroxy)acetyl]-1,2,3,4-tetrahydro-6-isoquinolinyl]-2-oxo-5-oxazolidinyl]methyl]ethanethioamide EXAMPLE 571 (+)-N-[[(5S)-3-[2-formyl-1,2,3,4-tetrahydro-7-isoquinolinyl]-2-oxo-5-oxazolidinyl]methyl]ethanethioamide, or EXAMPLE 572 (+)-N-[[(5S)-3-[2-[(hydroxy)acetyl]-1,2,3,4-tetrahydro-7-isoquinolinyl]-2-oxo-5-oxazolidinyl]methyl]ethanethioamide EXAMPLE 573 (−)-N-[[(5S)-3-(3,4-dihydro-1H-2-benzopyran-6-yl)-2-oxo-5-oxazolidinyl]methyl]acetamide EXAMPLE 574 (+)-N-[[(5S)-3-(3,4-dihydro-1H-2-benzopyran-6-yl)-2-oxo-5-oxazolidinyl]methyl]ethanethioamide EXAMPLE 575 (−)-N-[[(5S)-3-(3,4-dihydro-1H-2-benzothiopyran-6-yl)-2-oxo-5-oxazolidinyl]methyl]acetamide EXAMPLE 576 (+)-N-[[(5S)-3-(3,4-dihydro-1H-2-benzothiopyran-6-yl)-2-oxo-5-oxazolidinyl]methyl]ethanethioamide, or EXAMPLE 577 (+)-N-[[(5S)-3-(3,4-dihydro-2,2-dioxido-1H-2-benzothiopyran-6-yl)-2-oxo-5-oxazolidinyl]methyl]ethanethioamide EXAMPLE 578 (+)-N-[[(5S)-3-(3,4-dihydro-1H-2-benzopyran-7-yl)-2-oxo-5-oxazolidinyl]methyl]ethanethioamide EXAMPLE 579 (−)-N-[[(5S)-3-(3,4-dihydro-1H-2-benzothiopyran-7-yl)-2-oxo-5-oxazolidinyl]methyl]acetamide EXAMPLE 580 (+)-N-[[(5S)-3-(3,4-dihydro-1H-2-benzothiopyran-7-yl)-2-oxo-5-oxazolidinyl]methyl]ethanethioamide EXAMPLE 581 (+)-N-[[(5S)-3-(3,4-dihydro-2,2-dioxido-1H-2-benzothiopyran-7-yl)-2-oxo-5-oxazolidinyl]methyl]ethanethioamide, or EXAMPLE 582 N-[[(5S)-3-(3,4-dihydro-2-oxido-1H-2-benzothiopyran-7-yl)-2-oxo-5-oxazolidinyl]methyl]acetamide, EXAMPLE 583 N-{(5S)-3-(3-formyl-1,2,4,5-tetrahydro-1H-3-benzazepin-7-yl)-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide EXAMPLE 584 N-{[(5S)-3-(3-glycoloyl-1,2,4,5-tetrahydro-1H-3-benzazepin-7-yl)-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide EXAMPLE 585 N-{[(5S)-3-(3-glycoloyl-1,2,4,5-tetrahydro-1H-3-benzazepin-7-yl)-2-oxo-1,3-oxazolidin-5-yl]methyl}ethanethioamide EXAMPLE 586 N-{[(5S)-3-(3-acetyl-1,2,4,5-tetrahydro-1H-3-benzazepin-7-yl)-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide EXAMPLE 587 N-{[(5S)-3-(3-benzoyl-1,2,4,5-tetrahydro-1H-3-benzazepin-7-yl)-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide EXAMPLE 588 N-({(5S)-3-[3-(5-amino-1,3,4-thiadiazol-2-yl)-1,2,4,5-tetrahydro-1H-3-benzazepin-7-yl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide EXAMPLE 589 N-({(5S)-3-[3-(methylsulfonyl)-1,2,4,5-tetrahydro-1H-3-benzazepin-7-yl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide EXAMPLE 590 N-({(5S)-3-[3-(5-methylthio-1,3,4-thiadiazol-2-yl)-1,2,4,5-tetrahydro-1H-3-benzazepin-7-yl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide EXAMPLE 591 N-({(5S)-3-[3-(5-methyl-1,3,4-thiadiazol-2-yl)-1,2,4,5-tetrahydro-1H-3-benzazepin-7-yl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide, EXAMPLE 592 N-[((5S)-3-{3-(phenyl)acetyl-1,2,4,5-tetrahydro-1H-3-benzazepin-7-yl}-2-oxo-1,3-oxazolidin-5-yl)methyl]acetamide EXAMPLE 593 N-[((5S)-3-{3-[5-(formylamino)-1,3,4-thiadiazol-2-yl]-1,2,4,5-tetrahydro-1H-3-benzazepin-7-yl}-2-oxo-1,3-oxazolidin-5-yl)methyl]acetamide EXAMPLE 594 N-[5-(7-{(5S)-5-[(acetylamino)methyl]-2-oxo-1,3-oxazolidin-3-yl}-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl)-1,3,4-thiadiazol-2-yl]-2-hydroxyacetamide, EXAMPLE 595 N-[((SS)-3-{3-[(4-iodophenyl)acetyl]-1,2,4,5-tetrahydro-1H-3-benzazepin-7-yl}-2-oxo-1,3-oxazolidin-5-yl)methyl]acetamide EXAMPLE 596 N-[((5S)-3-{3-[(3-trifluoromethyl)phenyl)acetyl]-1,2,4,5-tetrahydro-1H-3-benzazepin-7-yl}-2-oxo-1,3-oxazolidin-5-yl)methyl]acetamide, EXAMPLE 597 N-[((5S)-3-{3-[(4-trifluoromethyl)phenyl)acetyl]-1,2,4,5-tetrahydro-1H-3-benzazepin-7-yl}-2-oxo-1,3-oxazolidin-5-yl)methyl]acetamide, EXAMPLE 598 N-({(5S)-2-oxo-3-[3-(5-oxopentanoyl)-1,2,4,5-tetrahydro-1H-3-benzazepin-7-yl]-1,3-oxazolidin-5-yl}methyl)acetamide EXAMPLE 599 N-({(5S)-2-oxo-3-[3-(5-oxohexanoyl)-1,2,4,5-tetrahydro-1H-3-benzazepin-7-yl]-1,3-oxazolidin-5-yl}methyl)acetamide, EXAMPLE 600 N-[{(5S)-3-(2-formyl-1,3,4,5-tetrahydro-1H-2-benzazepin-7-yl)-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide EXAMPLE 601 N-{[(5S)-3-(2-glycoloyl-1,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide EXAMPLE 602 N-{[(5S)-3-(2-acetyl-1,3,4,5-tetrahydro-1H-2-benzazepin-7-yl)-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide EXAMPLE 603 7-{(5S)-5-[(acetylamino)methyl]-2-oxo-1,3-oxazolidin-3-yl}-N-phenyl-1,3,4,5-tetrahydro-2H-2-benzazepine-2-carboxamide EXAMPLE 604 N-{[(5S)-3-(1-formyl-2,3,4,5-tetrahydro-1H-1-benzazepin-7-yl)-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide EXAMPLE 605 N-{[(SS)-3-(1-formyl-2,3,4,5-tetrahydro-1H-1-benzazepin-7-yl)-2-oxo-1,3-oxazolidin-5-yl]methyl}ethanethioamide EXAMPLE 606 N-[[(5S)-2-oxo-3-(1,2,4,5-tetrahydro-3-benzothiepin-7-yl)-5-oxazolidinyl]methyl]acetamide EXAMPLE 607 N-[[(5S)-2-oxo-3-(1,2,4,5-tetrahydro-3,3-dioxido-3-benzothiepin-7-yl)-5-oxazolidinyl]methyl]acetamide EXAMPLE 608 N-[[(5S)-2-oxo-3-(1,2,4,5-tetrahydro-3-benzothiepin-7-yl)-5-oxazolidinyl]methyl]ethanethioamide EXAMPLE 609 N-[[(5S)-2-oxo-3-(1,2,4,5-tetrahydro-3,3-dioxido-3-benzothiepin-7-yl)-5-oxazolidinyl]methyl]ethanethioamide EXAMPLE 610 N-({(5S)-3-[3-fluoro-4-(1-imino-1-oxido-1^(λ4),4-thiazinan-4-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)ethanethioamide EXAMPLE 611 N-({(5S)-3-[3-fluoro-4-(1-imino-1-oxido-1^(λ4),4-thiazinan-4-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)propanecarbothioamide EXAMPLE 612 N-({(5S)-3-[3-fluoro-4-(1-imino-1-oxido-1^(λ4),4-thiazinan-4-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)cyclopropanecarbothioamide EXAMPLE 613 N-({(5S)-3-[3-fluoro-4-(1-imino-1-oxidohexahydro-1^(λ4)-thiopyran-4-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide (E)-isomer EXAMPLE 614 N-({(5S)-3-[3-fluoro-4-(1-imino-1-oxidohexahydro-1^(λ4)-thiopyran-4-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)ethanethioamide (E)-isomer EXAMPLE 615 N-({(5S)-3-[3-fluoro-4-(1-imino-1-oxidohexahydro-1^(λ4)-thiopyran-4-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)propanethioamide (E)-isomer EXAMPLE 616 N-({(5S)-3-[3-fluoro-4-(1-imino-1-oxidohexahydro-1^(λ4)-thiopyran-4-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)cyclopropanecarbothioamide (E)-isomer, EXAMPLE 617 N-({(5S)-3-[3-fluoro-4-(1-imino-1-oxidohexahydro-1^(λ4)-thiopyran-4-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide (Z)-isomer EXAMPLE 618 N-({(5S)-3-[3-fluoro-4-(1-imino-1-oxidohexahydro-1^(λ4)-thiopyran-4-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)ethanethioamide (Z)-isomer EXAMPLE 619 N-({(5S)-3-[3-fluoro-4-(1-imino-1-oxidohexahydro-1^(λ4)-thiopyran-4-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)propanethioamide (Z)-isomer EXAMPLE 620 N-({(5S)-3-[3-fluoro-4-(1-imino-1-oxidohexahydro-1^(λ4)-thiopyran-4-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)cyclopropanethioamide (Z)-isomer EXAMPLE 621 N-({(5S)-3-[3-fluoro-4-[1-(acetylimino)-1-oxidohexahydro-1^(λ4)-thiopyran-4-yl]phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide, Z-isomer EXAMPLE 622 N-({(5S)-3-[3-fluoro-4-[1-(methylimino)-1-oxidohexahydro-1^(λ4)-thiopyran-4-yl]phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)propanethioamide, Z-isomer EXAMPLE 623 N-({(5S)-3-[3-fluoro-4-[1-(acetylimino)-1-oxidohexahydro-1^(λ4)-thiopyran-4-yl]phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)propanethioamide, Z-isomer EXAMPLE 624 N-({(5S)-3-[3-fluoro-4-[1-(ethylimino)-1-oxidohexahydro-1^(λ4)-thiopyran-4-yl]phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)propanethioamide, Z-isomer, EXAMPLE 625 N-({(5S)-3-[3-fluoro-4-[1-[(phenylmethyl)imino]-1-oxidohexahydro-1^(λ4)-thiopyran-4-yl]phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)propanethioamide, Z-isomer, EXAMPLE 626 N-({(5S)-3-[3-fluoro-4-[1-[(3-phenylpropyl)imino]-1-oxidohexahydro-1^(λ4)-thiopyran-4-yl]phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)propanethioamide, Z-isomer, EXAMPLE 627 N-({(5S)-3-[3-fluoro-4-(1-{([(methylamino)carbonyl]imino}-1-oxidohexahydro-1^(λ4)-thiopyran-4-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)propanethioamide, Z-isomer, EXAMPLE 628 N-({(5S)-3-[3-fluoro-4-(1-[(methoxycarbonyl)imino]-1-oxidohexahydro-1^(λ4)-thiopyran-4-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)propanethioamide, Z-isomer, EXAMPLE 629 N-({(5S)-3-[3-fluoro-4-(1-[[(ethoxycarbonyl)methyl]imino]-1-oxidohexahydro-1%-thiopyran-4-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)propanethioamide, Z-isomer, EXAMPLE 630 N-({(5S)-3-[3-fluoro-4-(1-{[[(4-nitrophenyl)amino]carbonyl]imino}-1-oxidohexahydro-1^(λ4)-thiopyran-4-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)propanethioamide, Z-isomer, EXAMPLE 631 N-({(5S)-3-[3-fluoro-4-[1-[(aminocarbonyl)imino]-1-oxidohexahydro-1^(λ4)-thiopyran-4-yl]phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)propanethioamide, Z-isomer, EXAMPLE 632 N-({(5S)-3-[3-fluoro-4-1^(λ4)-[[(aminocarbonyl)methyl]imino]-1-oxidohexahydro-1^(λ4)-thiopyran-4-yl]phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)propanethioamide, Z-isomer, EXAMPLE 633 N-({(5S)-3-[3-fluoro-4-[1-[(2-hydroxyethyl) imino]-1-oxidohexahydro-1^(λ4)-thiopyran-4-yl]phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)propanethioamide, Z-isomer, EXAMPLE 634 N-[((5S)-3-{3-fluoro-4-[1-(methylimino)-1-oxido-1^(λ4),4-thiazinan-4-yl]phenyl}-2-oxo-1,3-oxazolidin-5-yl)methyl]propanethioamide EXAMPLE 635 N-[((5S)-3-{3-fluoro-4-[1-(methylimino)-1-oxido-1^(λ4),4-thiazinan-4-yl]phenyl}-2-oxo-1,3-oxazolidin-5-yl) methyl]cyclopropanecarbothioamide EXAMPLE 636 N-[((5S)-3-{3-fluoro-4-(1-[(methoxycarbonyl)imino]-1-oxido-1^(λ4),4-thiazinan-4-yl)phenyl}-2-oxo-1,3-oxazolidin-5-yl)methyl]propanethioamide, EXAMPLE 637 N-[((5S)-3-{3-fluoro-4-(1-[(methoxycarbonyl)imino]-1-oxido-1^(λ4),4-thiazinan-4-yl)phenyl}-2-oxo-1,3-oxazolidin-5-yl)methyl]cyclopropanecarbothioamide, EXAMPLE 638 N-({(5S)-3-[3-fluoro-4-[1-(methylimino)-1-oxidohexahydro-1^(λ4)-thiopyran-4-yl]phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)cyclopropanecarbothioamide, Z-isomer, EXAMPLE 639 N-[((5S)-3-{3-fluoro-4-[1-[(methoxycarbonyl)imino]-1-oxidohexahydro-1-thiopyran-4-yl]phenyl}-2-oxo-1,3-oxazolidin-5-yl)methyl]cyclopropanecarbothioamide, Z-isomer, EXAMPLE 640 N-[((5S)-3-{3-fluoro-4-[1-(methylimino)-1-oxidohexahydro-1^(λ4)-thiopyran-4-yl]phenyl}-2-oxo-1,3-oxazolidin-5-yl)methyl]cyclopropanecarbothioamide, E-isomer, EXAMPLE 641 N-[((5S)-3-{3-fluoro-4-[1-(methylimino)-1-oxidohexahydro-1^(λ4)-thiopyran-4-yl]phenyl}-2-oxo-1,3-oxazolidin-5-yl)methyl]propanethioamide, E-isomer EXAMPLE 642 N-[((5S)-3-{3-fluoro-4-[1-[[(phenylmethoxy)carbnonyl]imino]-1-oxidohexahydro-1^(λ4)-thiopyran-4-yl]phenyl}-2-oxo-1,3-oxazolidin-5-yl)methyl]acetamide, Z-isomer, EXAMPLE 643 N-({(5S)-3-[3-Fluoro-4-(1-{[(benzylamino)carbonyl]imino}-1-oxidohexahydro-1^(λ4)-thiopyran-4-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide, Z-isomer, EXAMPLE 644 N-{[(5S)-3-(3-fluoro-4-{4-[2-(methylsulfinyl)acetyl]-1-piperazinyl}phenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl}propanethioamide EXAMPLE 645 N-{[(5S)-3-(3-fluoro-4-{4-[2-(methylsulfanyl)acetyl]-1-piperazinyl}phenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl}propanethioamide EXAMPLE 646 N-{[(5S)-3-(3-fluoro-4-{4-[2-(methylsulfonyl)acetyl]-1-piperazinyl}phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl}propanethioamide EXAMPLE 647 N-({(5S)-3-[4-(4-ethanethiolyl-1-piperazinyl)-3-fluorophenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)propanethioamide EXAMPLE 648 N-({(5S)-3-[4-(4-cyano-1-piperazinyl)-3-fluorophenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)propanethioamide EXAMPLE 649 N-({(5S)-3-(3-fluoro-4-{4-[2-(methylaminocarbonyloxy)acetyl]-1-piperazinyl}phenyl)-2-oxo-1,3-oxazolidin-5-yl}methyl)propanethioamide EXAMPLE 650 N-({(5S)-3-(3-fluoro-4-{4-[2-[(2-methoxyethoxy)carbonyloxy]acetyl]-1-piperazinyl}phenyl)-2-oxo-1,3-oxazolidin-5-yl}methyl)propanethioamide EXAMPLE 651 N-[((5S)-3-{3-fluoro-4-[4-((2S)-2-hydroxy-3-methoxypropanoyl)-1-piperazinyl]phenyl}-2-oxo-1,3-oxazolidin-5-yl)methyl]propanethioamide EXAMPLE 652 N-[((5S)-3-{3-fluoro-4-[4-((2S)-2,3-dimethyoxypropanoyl)-1-piperazinyl]phenyl}-2-oxo-1,3-oxazolidin-5-yl)methyl]propanethioamide EXAMPLE 653 N-[((5S)-3-{3-fluoro-4-[4-((2S)-3-hydroxy-2-methyoxypropanoyl)-1-piperazinyl]phenyl}-2-oxo-1,3-oxazolidin-5-yl)methyl]propanethioamide EXAMPLE 654 N-({(5S)-3-[3-fluoro-4-(4-acetoacetyl-1-piperazinyl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)propanethioamide EXAMPLE 655 N-({(5S)-3-[3-fluoro-4-(4-pyruvoyl-1-piperazinyl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)propanethioamide EXAMPLE 656 N-({(5S)-3-[3-fluoro-4-[4-(3-hydroxypropanoyl)-1-piperazinyl]phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl]propanethioamide EXAMPLE 657 N-{[(5S)-3-(3-fluoro-4-{4-[(1-hydroxycyclopropyl)carbonyl]-1-piperazinyl}phenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl}propanethioamide EXAMPLE 658 N-[((5S)-3-{3-fluoro-4-[4-(2-phenoxyacetyl)-1-piperazinyl]phenyl}-2-oxo-1,3-oxazolidin-5-yl)methyl]propanethioamide EXAMPLE 659 N-({(5S)-3-[3-fluoro-4-[4-((2S)-2,3-dihydroxypropanoyl)-1-piperazinyl]phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)propanethioamide EXAMPLE 660 N-({(5S)-3-[3-fluoro-4-[4-((2R)-2,3-dihydroxypropanoyl)-1-piperazinyl]phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)propanethioamide EXAMPLE 661 N-{[(5S)-3-(3-fluoro-4-{4-(3-hydroxy-2-(hydroxymethyl)-2-methylpropanoyl]-1-piperazinyl}phenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl}propanethioamide EXAMPLE 662 N-[((5S)-3-{3-fluoro-4-[4-((2S)-2-hydroxy-3-phenylpropanoyl)-1-piperazinyl]phenyl}-2-oxo-1,3-oxazolidin-5-yl)methyl]propanethioamide EXAMPLE 663 N-[((5S)-3-{3-fluoro-4-[4-((2R)-2-hydroxy-3-phenylpropanoyl)-1-piperazinyl]phenyl}-2-oxo-1,3-oxazolidin-5-yl) methyl]propanethioamide, EXAMPLE 664 N-[((5S)-3-{3-fluoro-4-[4-((2R)-2-hydroxy-2-phenylacetyl)-1-piperazinyl]phenyl}-2-oxo-1,3-oxazolidin-5-yl)methyl]propanethioamide EXAMPLE 665 N-[((5S)-3-{3-fluoro-4-[4-((2S)-2-acetoxy-2-phenylacetyl)-1-piperazinyl]phenyl}-2-oxo-1,3-oxazolidin-5-yl)methyl]propanethioamide

[0838] In order to more fully illustrate the nature of the invention and the manner of practicing the same, the following synthesis Example is presented.

SYNTHESIS EXAMPLE

[0839] 2-{(3-[Acetyl({(5S)-3-[4-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-3-fluorophenyl]-2-oxo-1,3-oxazolidin 5-yl}methyl)amino]-1,1-dimethyl-3-oxopropyl}-3,5-dimethylphenyl Dihydrogen Phosphate.

[0840] Step 1.

[0841] A stirred mixture of 2 (0.57 g, 1.18 mmol) (M. G. Nicolaou, C. -S. Yuan and R. T. Borchardt, J. Org. Chem. 1996, 61, 8636-8641), 3 (0.45 g, 1.19 mmol) (Case 6118.N CN1, Example 11, Step 1) and triethylamine (0.8 ml) in CH₂Cl₂ (60 ml), under nitrogen was cooled in an ice bath and treated with bis (2-oxo-3-oxazolidinyl)phosphinic chloride (0.456 g, 1.79 mmol). It was kept in the ice bath for 45 min and at ambient temperature (24° C.) for 2 h 15 min and then concentrated in vacuo. The residue was mixed with EtOAc and washed with 5% aqueous citric acid and brine, dried (MgSO₄) and concentrated. Chromatography of the residue on silica gel with 2.5% MeOH—CH₂Cl₂ gave 0.88 g of 4: ¹H NMR (300 MHz, CDCl₃) δ 1.61, 1.65 (s, s, 6H), 2.08 (s, 3H), 2.15 (m, 2H), 2.37 (m, 2H), 2.48 (s, 3H), 2.56 (m, 2H), 3.13 (m, 6H), 3.35 (m, 3H), 4.28 (m, 1H), 5.12 (m, 4H), 6.66 (s, 1H), 6.98 (s, 1H), 7.13 (m, 3H), 7.36 (m, 11H); MS (ESI) m/z 807 (M+H⁺), 829 (M+Na⁺)

[0842] Step 2.

[0843] A stirred solution of 4 (0.85 g, 1.05 mmol) in methyl trimethylsilylcarbamate (3 ml), under nitrogen was treated, dropwise with acetyl chloride (0.25 ml, 3.5 mmol) and kept at ambient temperature (24° C.) for 3.5 h. It was then diluted with pentane to give a gum. The liquid was decanted and the residue was trituratred twice with pentane and once with Et₂O to give a semisolid material that was chromatographed on silica gel with 30% EtOAc —CH₂Cl₂. The product amounted to 0.62 g of 5: ¹H NMR (300 MHz, CDCl₃) ^(δ) 1.55 (s, 3H), 1.62 (s, 3H), 2.16 (s, 3H), 2.20 (m, 1H), 2.23 (s, 3H), 2.42 (m, 2H), 2.57 (s, 3H), 3.17 (m, 5H), 3.52 (m, 5H), 3.87 (m, 2H), 4.61 (m, 1H), 5.05 (m, 4H), 6.79 (s, 1H), 6.98 (s, 1H), 7.11 (dd, 1H), 7.28 (m, 11H), 7.42 (dd, 1H); HRMS (FAB) calcd for C₄₄H₅₁FN₂O₁₀PS (M+H⁺), 849.2986, found 849.2988.

[0844] Step 3.

[0845] A mixture of 5 (0.62 g), 10% palladium-on-carbon catalyst (0.16 g) and THF (20 ml) was hydrogenated at atmospheric pressure for 80 min, filtered through celite and concentrated in vacuo. The resulting foam was triturated with Et₂O to give 0.419 g of 1, a white powder: mp 116-124° C. (dec); MS (ESI) m/z 627 (M+H⁺), 649 (M+Na⁺); HRMS (FAB) calcd for C₂₈H₃₇FN₂O₉PS (M+H⁺) 627.1941, found 627.1947.

[0846] Although the present invention has been exemplified using oxazolidinone compounds, it is understood that any amide-containing compound can be made more water-soluble using the present invention. Moreover, although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity and understanding, it would be apparent to those skilled in the art that certain changes and modifications could be made without departing from the scope and spirit of the present invention. As such, the description and example should not be construed as limiting the scope of the invention.

1 58 1 1796 DNA Homo sapiens 1 tcgacccacg cgtccggcgg atctgggaag cgcctcttca cggcactggg atccgcatct 60 gcctgggatc atcaagccct agaagctggg tttctttaaa ttagggctgc cgttttctgt 120 ttctccctgg gctgcggaaa gccagaagat tttatctagc ttatacaagg ctgctggtgt 180 tccctctttt ttttccacga gggtgttttt ggctgcaatt gcatgaaatc ccaatggtgt 240 agaccagtgg cgatggatct aggagtttac caactgagac atttttcaat ttctttcttg 300 tcatccttgc tggggactga aaacgcttct gtgagacttg ataatagctc ctctggtgca 360 agtgtggtag ctattgacaa caaaatcgag caagctatgg atctagtgaa aagccatttg 420 atgtatgcgg tcagagaaga agtggaggtc ctcaaagagc aaatcaaaga actaatagag 480 aaaaattccc agctggagca ggagaacaat ctgctgaaga cactggccag tcctgagcag 540 cttgcccagt ttcaggccca gctgcagact ggctcccccc ctgccaccac ccagccacag 600 ggcaccacac agccccccgc ccagccagca tcgcagggct caggaccaac cgcatagctg 660 cctatgcccc cgcagaactg gctgctgcgt gtgaactgaa cagacggaga agatgtgcta 720 gggagaatct gcctccacag tcacccattt cattgctcgc tgcgaaagag acgtgagact 780 gacatatgcc attatctctt ttccagtatt aaacactcat atgcttatgg cttggagaaa 840 tttcttagtt gggtgaatta aaggttaatc cgagaattag catggatata ccgggacctc 900 atgcagcttg gcagatatct gagaaatggt ttaattcatg ctcaggagct gtgtgccttt 960 ccatcccttc cggctcccta cccctcactt ccaagggttc tctctcctgc ttgcgcttag 1020 tgtcctacat ggggttgtga agcgatggag ctcctcactg gactcgcctc tctcctctcc 1080 tccccccagg aggaacttga aaggagggta aaaagactaa aatgaggggg aacagagttc 1140 actgtacaaa tttgacaact gtcaccaaaa ttcataaaaa acaatagtac tgtgcctctt 1200 tcttctcaaa caatggatga cacaaaacta tgagagtgac aaaatggtga caggtagctg 1260 ggacctaggc tatcttacca tgaaggttgt tttgcttatt gtatatttgt gtatgtagtg 1320 taactatttt gtacaataga ggactgtaac tactatttag gttgtacaga ttgaaattta 1380 gttgtttcat tggctgtctg aggaggtgtg gacttttata tatagatcta cataaaaact 1440 gctacatgac aaaaaccaca cctaaagaaa ttttaagaat ttggcacagt tactcacttt 1500 gtgtaatctg aaatctagct gctgaatacg ctgaagtaaa tccttgttca ctgaagtctt 1560 tcaattgagc tggttgaata ctttgaaaaa tgctcagttc taactaatga aatggatttc 1620 ccagtagggg tttctgcata tcacctgtat agtagttata tgcatatgtt tctgtgcatg 1680 ttctctacac aattgtaagg tgtcactgta tttaactgtt gcacttgtca actttcaata 1740 aagcatataa atgttgataa aaaaaaaaaa aaaaaaaaaa aaaaaaaagg gcggcc 1796 2 435 DNA Homo sapiens 2 atgaaatccc aatggtgtag accagtggcg atggatctag gagtttacca actgagacat 60 ttttcaattt ctttcttgtc atccttgctg gggactgaaa acgcttctgt gagacttgat 120 aatagctcct ctggtgcaag tgtggtagct attgacaaca aaatcgagca agctatggat 180 ctagtgaaaa gccatttgat gtatgcggtc agagaagaag tggaggtcct caaagagcaa 240 atcaaagaac taatagagaa aaattcccag ctggagcagg agaacaatct gctgaagaca 300 ctggccagtc ctgagcagct tgcccagttt caggcccagc tgcagactgg ctccccccct 360 gccaccaccc agccacaggg caccacacag ccccccgccc agccagcatc gcagggctca 420 ggaccaaccg catag 435 3 144 PRT Homo sapiens 3 Met Lys Ser Gln Trp Cys Arg Pro Val Ala Met Asp Leu Gly Val Tyr 1 5 10 15 Gln Leu Arg His Phe Ser Ile Ser Phe Leu Ser Ser Leu Leu Gly Thr 20 25 30 Glu Asn Ala Ser Val Arg Leu Asp Asn Ser Ser Ser Gly Ala Ser Val 35 40 45 Val Ala Ile Asp Asn Lys Ile Glu Gln Ala Met Asp Leu Val Lys Ser 50 55 60 His Leu Met Tyr Ala Val Arg Glu Glu Val Glu Val Leu Lys Glu Gln 65 70 75 80 Ile Lys Glu Leu Ile Glu Lys Asn Ser Gln Leu Glu Gln Glu Asn Asn 85 90 95 Leu Leu Lys Thr Leu Ala Ser Pro Glu Gln Leu Ala Gln Phe Gln Ala 100 105 110 Gln Leu Gln Thr Gly Ser Pro Pro Ala Thr Thr Gln Pro Gln Gly Thr 115 120 125 Thr Gln Pro Pro Ala Gln Pro Ala Ser Gln Gly Ser Gly Pro Thr Ala 130 135 140 4 405 DNA Homo sapiens 4 atggatctag gagtttacca actgagacat ttttcaattt ctttcttgtc atccttgctg 60 gggactgaaa acgcttctgt gagacttgat aatagctcct ctggtgcaag tgtggtagct 120 attgacaaca aaatcgagca agctatggat ctagtgaaaa gccatttgat gtatgcggtc 180 agagaagaag tggaggtcct caaagagcaa atcaaagaac taatagagaa aaattcccag 240 ctggagcagg agaacaatct gctgaagaca ctggccagtc ctgagcagct tgcccagttt 300 caggcccagc tgcagactgg ctccccccct gccaccaccc agccacaggg caccacacag 360 ccccccgccc agccagcatc gcagggctca ggaccaaccg catag 405 5 134 PRT Homo sapiens 5 Met Asp Leu Gly Val Tyr Gln Leu Arg His Phe Ser Ile Ser Phe Leu 1 5 10 15 Ser Ser Leu Leu Gly Thr Glu Asn Ala Ser Val Arg Leu Asp Asn Ser 20 25 30 Ser Ser Gly Ala Ser Val Val Ala Ile Asp Asn Lys Ile Glu Gln Ala 35 40 45 Met Asp Leu Val Lys Ser His Leu Met Tyr Ala Val Arg Glu Glu Val 50 55 60 Glu Val Leu Lys Glu Gln Ile Lys Glu Leu Ile Glu Lys Asn Ser Gln 65 70 75 80 Leu Glu Gln Glu Asn Asn Leu Leu Lys Thr Leu Ala Ser Pro Glu Gln 85 90 95 Leu Ala Gln Phe Gln Ala Gln Leu Gln Thr Gly Ser Pro Pro Ala Thr 100 105 110 Thr Gln Pro Gln Gly Thr Thr Gln Pro Pro Ala Gln Pro Ala Ser Gln 115 120 125 Gly Ser Gly Pro Thr Ala 130 6 261 DNA Homo sapiens 6 atggatctag tgaaaagcca tttgatgtat gcggtcagag aagaagtgga ggtcctcaaa 60 gagcaaatca aagaactaat agagaaaaat tcccagctgg agcaggagaa caatctgctg 120 aagacactgg ccagtcctga gcagcttgcc cagtttcagg cccagctgca gactggctcc 180 ccccctgcca ccacccagcc acagggcacc acacagcccc ccgcccagcc agcatcgcag 240 ggctcaggac caaccgcata g 261 7 86 PRT Homo sapiens 7 Met Asp Leu Val Lys Ser His Leu Met Tyr Ala Val Arg Glu Glu Val 1 5 10 15 Glu Val Leu Lys Glu Gln Ile Lys Glu Leu Ile Glu Lys Asn Ser Gln 20 25 30 Leu Glu Gln Glu Asn Asn Leu Leu Lys Thr Leu Ala Ser Pro Glu Gln 35 40 45 Leu Ala Gln Phe Gln Ala Gln Leu Gln Thr Gly Ser Pro Pro Ala Thr 50 55 60 Thr Gln Pro Gln Gly Thr Thr Gln Pro Pro Ala Gln Pro Ala Ser Gln 65 70 75 80 Gly Ser Gly Pro Thr Ala 85 8 237 DNA Homo sapiens 8 atgtatgcgg tcagagaaga agtggaggtc ctcaaagagc aaatcaaaga actaatagag 60 aaaaattccc agctggagca ggagaacaat ctgctgaaga cactggccag tcctgagcag 120 cttgcccagt ttcaggccca gctgcagact ggctcccccc ctgccaccac ccagccacag 180 ggcaccacac agccccccgc ccagccagca tcgcagggct caggaccaac cgcatag 237 9 78 PRT Homo sapiens 9 Met Tyr Ala Val Arg Glu Glu Val Glu Val Leu Lys Glu Gln Ile Lys 1 5 10 15 Glu Leu Ile Glu Lys Asn Ser Gln Leu Glu Gln Glu Asn Asn Leu Leu 20 25 30 Lys Thr Leu Ala Ser Pro Glu Gln Leu Ala Gln Phe Gln Ala Gln Leu 35 40 45 Gln Thr Gly Ser Pro Pro Ala Thr Thr Gln Pro Gln Gly Thr Thr Gln 50 55 60 Pro Pro Ala Gln Pro Ala Ser Gln Gly Ser Gly Pro Thr Ala 65 70 75 10 51 DNA Homo sapiens 10 atgcggtcag agaagaagtg gaggtcctca aagagcaaat caaagaacta a 51 11 16 PRT Homo sapiens 11 Met Arg Ser Glu Lys Lys Trp Arg Ser Ser Lys Ser Lys Ser Lys Asn 1 5 10 15 12 36 DNA Homo sapiens 12 atgcccccgc agaactggct gctgcgtgtg aactga 36 13 11 PRT Homo sapiens 13 Met Pro Pro Gln Asn Trp Leu Leu Arg Val Asn 1 5 10 14 27 DNA Homo sapiens 14 atgccattat ctcttttcca gtattaa 27 15 8 PRT Homo sapiens 15 Met Pro Leu Ser Leu Phe Gln Tyr 1 5 16 36 DNA Homo sapiens 16 atgcttatgg cttggagaaa tttcttagtt gggtga 36 17 11 PRT Homo sapiens 17 Met Leu Met Ala Trp Arg Asn Phe Leu Val Gly 1 5 10 18 30 DNA Homo sapiens 18 atggcttgga gaaatttctt agttgggtga 30 19 9 PRT Homo sapiens 19 Met Ala Trp Arg Asn Phe Leu Val Gly 1 5 20 159 DNA Homo sapiens 20 atggatatac cgggacctca tgcagcttgg cagatatctg agaaatggtt taattcatgc 60 tcaggagctg tgtgcctttc catcccttcc ggctccctac ccctcacttc caagggttct 120 ctctcctgct tgcgcttagt gtcctacatg gggttgtga 159 21 52 PRT Homo sapiens 21 Met Asp Ile Pro Gly Pro His Ala Ala Trp Gln Ile Ser Glu Lys Trp 1 5 10 15 Phe Asn Ser Cys Ser Gly Ala Val Cys Leu Ser Ile Pro Ser Gly Ser 20 25 30 Leu Pro Leu Thr Ser Lys Gly Ser Leu Ser Cys Leu Arg Leu Val Ser 35 40 45 Tyr Met Gly Leu 50 22 120 DNA Homo sapiens 22 atgcagcttg gcagatatct gagaaatggt ttaattcatg ctcaggagct gtgtgccttt 60 ccatcccttc cggctcccta cccctcactt ccaagggttc tctctcctgc ttgcgcttag 120 23 39 PRT Homo sapiens 23 Met Gln Leu Gly Arg Tyr Leu Arg Asn Gly Leu Ile His Ala Gln Glu 1 5 10 15 Leu Cys Ala Phe Pro Ser Leu Pro Ala Pro Tyr Pro Ser Leu Pro Arg 20 25 30 Val Leu Ser Pro Ala Cys Ala 35 24 174 DNA Homo sapiens 24 atgctcagga gctgtgtgcc tttccatccc ttccggctcc ctacccctca cttccaaggg 60 ttctctctcc tgcttgcgct tagtgtccta catggggttg tgaagcgatg gagctcctca 120 ctggactcgc ctctctcctc tcctcccccc aggaggaact tgaaaggagg gtaa 174 25 57 PRT Homo sapiens 25 Met Leu Arg Ser Cys Val Pro Phe His Pro Phe Arg Leu Pro Thr Pro 1 5 10 15 His Phe Gln Gly Phe Ser Leu Leu Leu Ala Leu Ser Val Leu His Gly 20 25 30 Val Val Lys Arg Trp Ser Ser Ser Leu Asp Ser Pro Leu Ser Ser Pro 35 40 45 Pro Pro Arg Arg Asn Leu Lys Gly Gly 50 55 26 12 DNA Homo sapiens 26 atggggttgt ga 12 27 3 PRT Homo sapiens 27 Met Gly Leu 1 28 81 DNA Homo sapiens 28 atggagctcc tcactggact cgcctctctc ctctcctccc cccaggagga acttgaaagg 60 agggtaaaaa gactaaaatg a 81 29 26 PRT Homo sapiens 29 Met Glu Leu Leu Thr Gly Leu Ala Ser Leu Leu Ser Ser Pro Gln Glu 1 5 10 15 Glu Leu Glu Arg Arg Val Lys Arg Leu Lys 20 25 30 66 DNA Homo sapiens 30 atgaggggga acagagttca ctgtacaaat ttgacaactg tcaccaaaat tcataaaaaa 60 caatag 66 31 21 PRT Homo sapiens 31 Met Arg Gly Asn Arg Val His Cys Thr Asn Leu Thr Thr Val Thr Lys 1 5 10 15 Ile His Lys Lys Gln 20 32 21 DNA Homo sapiens 32 atggatgaca caaaactatg a 21 33 6 PRT Homo sapiens 33 Met Asp Asp Thr Lys Leu 1 5 34 102 DNA Homo sapiens 34 atgacacaaa actatgagag tgacaaaatg gtgacaggta gctgggacct aggctatctt 60 accatgaagg ttgttttgct tattgtatat ttgtgtatgt ag 102 35 33 PRT Homo sapiens 35 Met Thr Gln Asn Tyr Glu Ser Asp Lys Met Val Thr Gly Ser Trp Asp 1 5 10 15 Leu Gly Tyr Leu Thr Met Lys Val Val Leu Leu Ile Val Tyr Leu Cys 20 25 30 Met 36 21 DNA Homo sapiens 36 atgagagtga caaaatggtg a 21 37 6 PRT Homo sapiens 37 Met Arg Val Thr Lys Trp 1 5 38 75 DNA Homo sapiens 38 atggtgacag gtagctggga cctaggctat cttaccatga aggttgtttt gcttattgta 60 tatttgtgta tgtag 75 39 24 PRT Homo sapiens 39 Met Val Thr Gly Ser Trp Asp Leu Gly Tyr Leu Thr Met Lys Val Val 1 5 10 15 Leu Leu Ile Val Tyr Leu Cys Met 20 40 39 DNA Homo sapiens 40 atgaaggttg ttttgcttat tgtatatttg tgtatgtag 39 41 12 PRT Homo sapiens 41 Met Lys Val Val Leu Leu Ile Val Tyr Leu Cys Met 1 5 10 42 66 DNA Homo sapiens 42 atgacaaaaa ccacacctaa agaaatttta agaatttggc acagttactc actttgtgta 60 atctga 66 43 21 PRT Homo sapiens 43 Met Thr Lys Thr Thr Pro Lys Glu Ile Leu Arg Ile Trp His Ser Tyr 1 5 10 15 Ser Leu Cys Val Ile 20 44 18 DNA Homo sapiens 44 atgctcagtt ctaactaa 18 45 5 PRT Homo sapiens 45 Met Leu Ser Ser Asn 1 5 46 21 DNA Homo sapiens 46 atgaaatgga tttcccagta g 21 47 6 PRT Homo sapiens 47 Met Lys Trp Ile Ser Gln 1 5 48 87 DNA Homo sapiens 48 atggatttcc cagtaggggt ttctgcatat cacctgtata gtagttatat gcatatgttt 60 ctgtgcatgt tctctacaca attgtaa 87 49 28 PRT Homo sapiens 49 Met Asp Phe Pro Val Gly Val Ser Ala Tyr His Leu Tyr Ser Ser Tyr 1 5 10 15 Met His Met Phe Leu Cys Met Phe Ser Thr Gln Leu 20 25 50 39 DNA Homo sapiens 50 atgcatatgt ttctgtgcat gttctctaca caattgtaa 39 51 12 PRT Homo sapiens 51 Met His Met Phe Leu Cys Met Phe Ser Thr Gln Leu 1 5 10 52 33 DNA Homo sapiens 52 atgtttctgt gcatgttctc tacacaattg taa 33 53 10 PRT Homo sapiens 53 Met Phe Leu Cys Met Phe Ser Thr Gln Leu 1 5 10 54 21 DNA Homo sapiens 54 atgttctcta cacaattgta a 21 55 6 PRT Homo sapiens 55 Met Phe Ser Thr Gln Leu 1 5 56 45 DNA Homo sapiens 56 atgttgataa aaaaaaaaaa aaaaaaaaaa aaaaaaaagg gcggc 45 57 15 PRT Homo sapiens 57 Met Leu Ile Lys Lys Lys Lys Lys Lys Lys Lys Lys Lys Gly Gly 58 289 DNA Homo sapiens 58 ctagcagatc tcccagtcac gacgttctaa aacgacggcc agtgcctagc ttataatacg 60 actcactata gggagagagc tatgacgtcg catgcacgcg taagcttggg cccctcgagg 120 gatcctctag agcggccgcc ggacgcgtgg gtcgacccgg gaattccgga ccggtacctg 180 caggcgtacc ttctatagtg tcacctaaat agctttttgc aaaagcctag tggtcatagc 240 tgtttcctgt gtgaaattgt tatccgctcc gcggcctagg ctagagtcc 289 

What is claimed is:
 1. An oxazolidinone derivative of formula (I)

wherein J is O or S;

R₂₁₀ is

R₃₁₀, R₄₁₀ and R₅₁₀ each independently are a) H, b) C₁₋₄ alkyl, c) halogen, d) C₁₋₄ alkoxy, e) hydroxy, f) (CH₂)_(c)OP(O)(OH)₂, g) C₁₋₄ acyloxy, or h) C₁₋₄ alkyl substituted by halogen, hydroxy, acyloxy, NR₁₂₁₀R₁₃₁₀, or alkoxy; R₆₁₀, R₇₁₀ and R₈₁₀ each independently are a) H, b) CH₃, or c) C₂H₅; R₉₁₀ and R₁₀₁₀ each independently are a) H, b) CH₃, c) C₂H₅, or d) combine to form a C₃₋₅ cycloalkyl; R₁₁₁₀ is H or C₁₋₆ alkyl; R₁₂₁₀ and R₁₃₁₀ each independently are a) H, b) C₁₋₄ alkyl, or c) combine to form a heterocyclic ring; wherein a is 0 or 1, b is 0 or 1, and c is 0 or 1, with the proviso that when Q′ is

 b is 0 and a+b is 0 or 1; R₁ is a) C₁₋₄ alkyl, b) C₂₋₄ alkenyl, c) OC₁₋₄ alkyl, d) C₃₋₆ cycloalkyl, e) C₁₋₄ alkyl substituted with 1-3F, 1-2Cl, CN, —COOC₁₋₄ alkyl or a C₃₋₆ cycloalkyl; or f) H A is

R₄ is a) C₁₋₄ alkyl optionally substituted with one or more halos, OH, CN, NR₁₀R₁₁, or —CO₂R₁₃, b) C₂₋₄ alkenyl, c) —NR₁₆R₁₈, d) —N₃, e) —NHC(═O)R₇, f) —NR₂₀C(═O)R₇, g) —N(R₁₉)₂, h) —NR₁₆R₁₉, or i) —NR₁₉R₂₀, R₅ and R₆ at each occurrence are the same or different and are a) C₁₋₂ alkyl, or b) R₅ and R₆ taken together are —(CH₂)_(k)—; R₇ is C₁₋₄ alkyl optionally substituted with one or more halos; R₁₀ and R₁₁ at each occurrence are the same or different and are a) H, b) C₁₋₄ alkyl, or c) C₃₋₈ cycloalkyl; R₁₃ is a) H, or b) C₁₋₄ alkyl; R₁₄ and R₁₅ at each occurrence are the same or different and are a) C₁₋₄ alkyl, or b) R₁₄ and R₁₅ taken together are —(CH)_(l)—; R₁₆ is a) H, b) C₁₋₄ alkyl, or c) C₃₋₈ cycloalkyl; R₁₇ is a) C₁₋₄ alkyl, or b) C₃₋₈ cycloalkyl; R₁₈ is a) H, b) C₁₋₄ alkyl, c) C₂₋₄ alkenyl, d) C₃₋₄ cycloalkyl, e) —OR₁₃ or f) —NR₂₁R₂₂; R₁₉ is a) Cl, b) Br, or c) I; R₂₀ is a physiologically acceptable cation; R₂₁ and R₂₂ at each occurrence are the same or different and are a) H, b) C₁₋₄ alkyl, or c) —NR₂₁R₂₂ taken together are —(CH₂)_(m)—; wherein R₂₃ and R₂₄ at each occurrence are the same or different and are a) H, b) F, c) Cl, d) C₁₋₂ alkyl, e) CN f) OH, g) C₁₋₂ alkoxy, h) nitro, or i) amino; Q is

m) a diazinyl group optionally substituted with X and Y, n) a triazinyl group optionally substituted with X and Y, o) a quinolinyl group optionally substituted with X and Y. p) a quinoxalinyl group optionally substituted with X and Y, q) a naphthyridinyl group optionally substituted with X and Y,

Q and R₂₄ taken together are

wherein Z¹ is a) —CH₂—, b) —CH(R¹⁰⁴)—CH₂—, c) —C(O)—, or d) —CH₂CH₂CH₂—; wherein Z² is a) —O₂S—, b) —O—, c) —N(R¹⁰⁷)—, d) —OS—, e) —S—, or f) S(O)(NR₁₉₀) wherein Z³ is a) —O₂S—, c) —OS—, d) —S—, or e) S(O)(NR₁₉₀) wherein A¹ is a) H—, or b) CH₃; wherein A is a) H—, b) HO—, c) CH₃—, d) CH₃O—, e) R¹⁰²O—CH₂—C(O)—NH— f) R¹⁰³O—C(O)—NH—, g) (C₁-C₂)alkyl-O—C(O)—, h) HO—CH₂—, i) CH₃O—NH—, j) (C₁-C₃)alkyl-O₂C— k) CH₃—C(O)—, l) CH₃—C(O)—CH₂—,

A¹ and A² taken together are:

wherein R¹⁰² is a) H—, b) CH₃—, c) phenyl-CH₂—, or d) CH₃C(O)—; wherein R¹⁰³ is a) (C₁-C₃)alkyl-, or b) phenyl-; wherein R¹⁰⁴ is a) H—, or b) HO—; wherein R¹⁰⁶ is a) CH₃—C(O)—, b) H—C(O)— c) Cl₂CH—C(O)—, d) HOCH₂—C(O)— e) CH₃SO₂—,

g) F2CHC(O)—,

i) H₃C—C(O)—O—CH₂—C(O)—, j) H—C(O)—O—CH₂—C(O)—,

l) HC≡C—CH₂O—CH₂—C(O)—, or m) phenyl-CH₂—O—CH₂—C(O)— wherein R₁₀₇ is a) R¹⁰²O—C(R₁₁₀)(R¹¹¹)—C(O)—, b) R¹⁰³O—C(O)— c) R₁₀₈—C(O)

f) H₃C—C(O)—(CH₂)₂—C(O)—, g) R¹⁰⁹—SO₂—,

i) HO—CH₂—C(O)—, j) R¹¹⁶—(CH₂)₂—, k) R¹¹³—C(O)—O—CH₂—C(O)—, l) (CH₃)₂N—CH₂—C(O)—NH—, m) NC—CH₂—, n) F₂—CH—CH₂—, or o) R¹⁵⁰R¹⁵¹NSO₂ p) C(O)CR₁₈₀R₁₈₀R₁₈₁OR₁₈₂, q) C(O)CH₂S(O)_(i)CH₃, r) C(O)CH₂S(O)(NR₁₈₃)CH₃, s) C(S)R₁₈₄, t) C(O)CH₂OR₁₈₅, u) C(O)(CH₂)₃C(O)CH₃, v) C(O)(CH₂OH)₂CH₃, w) C(O)CH₂CH₂OR₁₈₉, or x) —CN; wherein R¹⁰⁸ is a) H—, b) (C₁-C₄)alkyl, c) aryl —(CH₂) p, d) ClH₂C—, e) Cl₂HC—, f) FH₂C—, g) F₂HC—, h) (C₃-C₆)cycloalkyl, or i) CNCH₂—. wherein R¹⁰⁹ is a) alkylC₁-C₄, b) —CH₂Cl c) —CH₂CH═CH₂, d) aryl, or e) —CH₂CN; wherein R¹¹⁰ and R¹¹¹ are independently a) H—, b) CH₃—; or wherein R¹¹² is a) H—, b) CH₃O—CH₂O—CH₂—, or c) HOCH₂—; wherein R¹¹³ is a) CH₃—, b) HOCH₂—, c) (CH₃)₂N-phenyl, or d) (CH₃)₂N—CH₂—; wherein R¹¹⁴ is a) HO—, b) CH₃O—, c) H₂N—, d) CH₃O—C(O)—O—, e) CH₃—C(O)—O—CH₂—C(O)—O—, f) phenyl-CH₂—O—CH₂—C(O)—O—, g) HO—(CH₂)₂—O—, h) CH₃O—CH₂—O—(CH₂)₂—O—, or i) CH₃O—CH₂—O—; wherein R¹¹⁵ is a) H—, or b) Cl—; wherein R¹¹⁶ is a) HO— b) CH₃O—, or c) F; wherein R¹⁵⁰ and R¹⁵¹ are each H or alkyl C₁-C₄ or R¹⁵⁰ and R¹⁵¹ taken together with the nitrogen atom to which each is attached form a monocyclic heterocyclic ring having from 3 to 6 carbon atoms; R₁₅₂ is a) H, b) C₁₋₄alkyl, c) C₁₋₄heteroalkyl, d) (CH₂)_(l)C(═O)OC₁₋₄alkyl, e) (CH₂)_(l)C(═O)C₁₋₄alkyl, f) aryl, or g) het¹; R₁₅₃ and R₁₅₄ are independently a) H, b) F, c) C₁₋₄alkyl, d) C₃₋₆cycloalkyl, e) C₁₋₄heteroalkyl, f) aryl, g) het¹, h) OC₁₋₄alkyl, i) O(C═O)C₁₋₄alkyl, j) (C═O)OC₁₋₄alkyl; or k) R₁₅₃ and R₁₅₄ taken together are C₃₋₆cycloalkyl; R₁₅₅ is a) H, b) F, c) C₁₋₄alkyl, d) OC₁₋₄alkyl, e) SC₁₋₄alkyl, or f) NHC₁₋₄alkyl; R₁₅₆ is a) H, b) C₁₋₄alkyl, c) OC₁₋₄alkyl, d) SC₁₋₄alkyl, or e) NHC₁₋₄alkyl; R₁₅₇ is a) —H, b) —F, c) —Cl, d) —NH₂, e) —OH, f) —CN, g) —C₁₋₄alkyl, h) —OC₁₋₄alkyl, i) —C₁₋₄alkyl-W—C₁₋₄alkyl, j) —NHC₁₋₄alkyl, k) —(CH₂)_(i)C₃₋₆cycloalkyl, l) —C(═O)C₁₋₄alkyl, m) —OC(═O)C₁₋₄alkyl, n) —C(═O)OC₁₋₄alkyl, o) —S(O)_(i)C₁₋₄alkyl, or p) —C(═O)NHC₁₋₄alkyl; R₁₅₈ is a) —H, b) —CH₃, c) —F, or d) —OH; R₁₅₉ is a) —H, b) —C₁₋₄alkyl, c) —C(═O)C₁₋₄alkyl, d) —C(═O)NHC₁₋₄alkyl, e) —OC(═O)C₁₋₄alkyl, f) —C(═O)OC₁₋₄alkyl, or g) —S(O)_(l)C₁₋₄alkyl, or h) —C₁₋₄alkyl-W₁—C₁₋₄alkyl; R₁₆₀ is H, C₂₋₆ alkenyl, C₂₋₇alkynyl, C₁₋₆ alkyl substituted with one or two of the following: a) F, b) Cl, c) CF₃, d) —OH, e) C₁₋₄alkoxy, f) —CH₂C(═O)C₁₋₄alkyl, g) —OC(═O)N(R₁₆₁)₂, h) C₁₋₄alkyl S(O), (wherein n is 0, 1 or 2), i) —CN, j) carboxy, k) —C₁₋₄alkoxycarbonyl, l) —C(═O)N(R₁₆₁)₂, m) —N(R₁₆₁)SO₂C₁₋₄ alkyl, n) —N(R₁₆₁)C(═O)C₁₋₄ alkyl, o) —N(R₁₆₁)C(═O)N(R₄)₂, p) —N(R₁₆₁)C(═O)C₁₋₄ alkoxy, q) aryl, or r) Het₁; R₁₆₁ is a) H, or b) C₁₋₃ alkyl; R₁₆₂ is a) H, b) C₁₋₈ alkyl, optionally substituted with one to three F, Cl, OH, CN, NH₂, OC(═O)C₁₋₄alkyl, or OC₁₋₄ alkyl, c) C₃₋₈ alkene, or d) C(═O)NR₁₆₃R₁₆₄; R₁₆₃ and R₁₆₄ are independently a) H, or b) C₁₋₈ alkyl, optionally substituted with one to three F, Cl, OH, CN, or NH₂; R₁₆₅ is C₁₋₄ alkyl, optionally substituted with 1-3 R₁₆₈; R₁₆₆ is a) C₁₋₈ alkyl, optionally substituted with 1-3 halo, CN, NO₂, OH, SH or NH₂, b) —C(═O)R₁₆₇ or c) —C(═S)NHC₁₋₄ alkyl; R₁₆₇ is a) H, b) C₁₋₆ alkyl, optionally substituted with OH, C₁₋₄ alkoxy, NH₂, SH or halo, or c) —CH₂OC(═O)C₁₋₄ alkyl; R₁₆₈ is j) halo, k) —CN, l) —OH, m) —SH, n) —NH₂, o) —OR₁₆₉, p) —NHR₁₆₉, q) —N(R₁₆₉)₂, or r) —S(═O)_(i)R₁₆₉; R₁₆₉ is g) C₁₋₆ alkyl, h) —C(═O)C₁₋₄ alkyl, i) —C(═O)O C₁₋₄ alkyl, j) —C(═O)NH₂, k) —C(═O)NH C₁₋₄ alkyl, or l) —SO₂C₁₋₄ alkyl; with the proviso that where j is 0, Y₂ is —CH₂—. R₁₇₀ is a) H, b) C₁₋₁₂ alkyl, optionally substituted with phenyl or CN, or c) C₂₋₁₂ alkyl substituted with OH, SH, NH₂, —OC₁₋₆ alkyl, —NHC₁₋₆ alkyl, —NHCOC₁₋₆ alkyl, —NHSO₂C₁₋₆ alkyl, —S(O)_(l)C₁₋₆ alkyl, or one to three halo; R₁₇₂ is a) H, b) C₁₋₈ alkyl, c) aryl, d) het₁, e) C(=w)R₁₇₄, f) C(═O)OR₁₇₅, or g) S(═O)_(i)R₁₇₆; R₁₇₃ is a) H, or b) C₁₋₈ alkyl; R₁₇₄ is a) H, b) aryl, c) het₁, d) NR₁₇₇R₁₇₈, or e) C₁₋₈ alkyl; R₁₇₅ is a) C₁₋₈ alkyl, b) aryl, or c) het₁; R₁₇₆ is a) aryl, b) het₁, c) NR₁₇₇R₁₇₈, or d) C₁₋₈ alkyl; R₁₇₇ and R₁₇₈ are independently a) H, b) C₁₋₈ alkyl, or c) aryl; R₁₈₀ and R₁₈₁ taken together form C₃₋₅ cycloalkyl; R₁₈₂ is H, CH₃ or C₁₋₄ alkanoyl; R₁₈₃ is H, C₁₋₄ alkyl, C₁₋₄ alkanoyl, —C(═O)NH—C₁₋₄ alkyl or —CO₂C₁₋₄ alkyl; R₁₈₄ is C₁₋₄ alkyl, CH₂OR₁₈₆, S—C₁₋₄ alkyl, OC₁₋₄ alkyl, or NR₁₈₇R₁₈₈; R₁₈₅ is phenyl, —CO₂— (CH₂)₂—OCH₃, —P(═O)(OH)₂, —C(═O)—NR₁₈₇R₁₈₆, or —C(═O)—(CH₂)₂—CO₂H; R₁₈₆ is H, phenyl, benzyl, CH₃ or C(═O)CH₃; R₁₈₇ and R₁₈₈ are independently H or C₁₋₃ alkyl; or R₁₈₇ and R₁₈₈ taken together form a 5- or 6-membered saturated heterocycle, wherein said saturated heterocycle may further contain one or two additional hetero-atoms selected from a group consisting of O, S(O)_(n) or NR₁₈₂; R₁₈₉ is H, CH₃ or benzyl; R₁₉₀ is a) H, b) C₁₋₄ alkyl, c) C(═O)C₁₋₄ alkyl, d) C(═O)OC₁₋₄ alkyl, e) C(═O)NHR₁₉₁, or f) C(═S)NHR₁₉₁; R₁₉₁ is H, C₁₋₄ alkyl, or phenyl; at each occurrence, alkyl in R₁₉₀ and R₁₉₁ is optionally substituted with one or more halo, CN, NO₂, phenyl, C₃₋₆ cycloalkyl, OR₁₉₂, C(═O)R₁₉₂, OC(═O)R₁₉₂, C(═O)OR₁₉₂, SC(═O)_(i)R₁₉₂, S(═O)_(i)NR₁₉₂R₁₉₂, NR₁₉₂R₁₉₂, NR₁₉₂SO₂R₁₉₂, NR₁₉₂SO₂R₁₉₂R₁₉₂, NR₁₉₂C(═O)R₁₉₂, C(═O)NR₁₉₂R₁₉₂, NR₁₉₂R₁₉₂, oxo or oxime; R₁₉₂ is H, C₁₋₄ alkyl, or phenyl; at each occurrence, phenyl in R₁₉₁ and R₁₉₂ is optionally substituted with one or more halo, CN, NO₂, phenyl, C₃₋₆ cycloalkyl, OR₁₉₂, C(═O)R₁₉₂, OC(═O)R₁₉₂, C(═O)OR₁₉₂, S(═O)_(i)R₁₉₆, S(═O)_(l)NR₁₉₂R₁₉₂, NR₁₉₂SO₂R₁₉₂, NR₁₉₂SO₂NR₁₉₂R₁₉₂, NR₁₉₂C(═O)R₁₉₂, C(═O)NR₁₉₂R₁₉₂, or NR₁₉₂R₁₉₂; R₁₉₃ is selected from the group consisting of null, H, C₁-C₄alkyl, C₃-C₅cycloalkyl, C₁-C₄haloalkyl, and halophenyl; R₁₉₄ is selected from the group consisting of H, alkyl, C₁-C₂alkoxy, halo, and haloalkoxy, or R₁₉₃ and R₁₉₄ can be taken together to form a 5- or 6-membered, optionally substituted, heteroalkyl or heteroaryl ring; R₁₉₅ is H or F; R₁₉₆ is selected from the group consisting of H, methyl, amino, and F; R₁₉₇ is H, CH₃, or F; B is an unsaturated 4-atom linker having one nitrogen and three carbons; M is a) H, b) C₁₋₈ alkyl, c) C₃₋₈ cycloalkyl, d) —(CH₂)_(m)OR₁₃, or e) —(CH₂)_(h)—NR₂₁R₂₂; Z is a) O, b) S, or c) NM; W is a) CH, b) N, or c) S or O when Z is NM; Y is a) H, b) F, c) Cl, d) Br, e) C₁₋₃ alkyl, or f) NO₂; X is a) H, b) —CN, c) OR₂₇, d) halo, e) NO₂, f) tetrazoyl, g) —SH, h) —S(═O)_(i)R₄, i) —S(═O)₂—N═S(O)_(j)R₅R₆, j) —SC(═O)R₇, k) —C(═O)R₂₅, l) —C(═O)NR₂₇R₂₈, m) —C(═NR₂₉)R₂₅, n) —C(R₂₅)(R₂₈)—OR₁₃, o) —C(R₂₅)(R₂₈)—OC(═O)R₁₃, p) —C(R₂₈)(OR₁₃)—(CH₂)_(h)—NR₂₇R₂₈, q) —NR₂₇R₂₈, r) —N(R₂₇)C(═O)R₇, s) —N(R₂₇)—S(═O)_(l)R₇, t) —C(OR₁₄)(OR₁₅)R₂₈, u) —C(R₂₅)(R₁₆)—NR₂₇R₂₆, or v) C₁₋₈ alkyl substituted with one or more halos, OH, ═O other than at alpha position, —S(═O)_(i)R₁₇, —NR₂₇R₂₈, C₂₋₅ alkenyl, C₂₋₅ alkynyl, or C₃₋₈ cycloalkyl; X₁ is N or CR₁₅₈; Y₁ is a) S(O)_(i), b) S(NR₁₅₉), or c) S(NR₁₅₉)(O); W₁ is O or S; X₂ is O or NR₁₆₂; X₃ is S(O)_(i) or NR₁₆₆; Y₂ is a) O b) NH, c) CH₂, or d) S(O)_(i); X₄ is a) O b) NR₁₇₂, c) S(O)_(l), or d) S(O)(NR₁₇₃); and Y₃ is CH or N; R₄, R₅, R₆, R₇, R₁₃, R₁₄, R₁₅, R₁₆, and R₁₇ are the same as defined above; R₂₅ is a) H, b) C₁₋₈ alkyl optionally substituted with one or more halos, C₃₋₈ cycloalkyl, C₁₋₄ alkyl substituted with one or more of —S(═O)_(i)R₁₇, —OR₁₃, or OC(═O)R₁₃, NR₂₇R₂₈, or c) C₂₋₅ alkenyl optionally substituted with CHO, or CO₂R₁₃; R₂₆ is a) R₂₈, or b) NR₂₇NR₂₈; R₂₇ and R₂₈ at each occurrence are the same or different and are a) H, b) C₁₋₈ alkyl, c) C₃₋₈ cycloalkyl, d) —(CH₂)_(m)OR₁₃, e) —(CH₂)_(h)—NR₂₁R₂₂, or f) R₂₇ and R₂₈ taken together are —(CH₂)₂O(CH₂)₂—, (CH₂)_(h)CH(COR₇)—, or —(CH₂)₂N(CH₂)₂(R₇); R₂₉ is a) —NR₂₇R₂₈, b) —OR₂₇, or c) —NHC(═O)R₂₈; wherein R₃₀ is a) H, b) C₁₋₈ alkyl optionally substituted with one or more halos, or c) C₁₋₈ alkyl optionally substituted with one or more OH, or C₁₋₆ alkoxy; wherein E is a) NR₃₉, b) —S(═O)_(i), c) O, or d) S(O)(NR₁₉₀) R₃₈ is a) H, b) C₁₋₆ alkyl, c) —(CH₂)_(q)-aryl, or d) halo; R₃₉ is a) H, b) C₁₋₆ alkyl optionally substituted with one or more OH, halo, or —CN, c) —(CH₂)_(q)-aryl, d) —CO₂R₄₀, e) —COR₄₁, f) —C(═O)—(CH₂)_(q)—C(═O)R₄₀, g) —S(═O)₂—C₁₋₆ alkyl, h) —S(═O)₂— (CH₂)_(q)-aryl, or i) —(C═O)_(j)-Het; R₄₀ is a) H, b) C₁₋₆ alkyl optionally substituted with one or more OH, halo, or —CN, c) —(CH₂)_(q)-aryl, or d) —(CH₂)_(q)—OR₄₂; R₄₁ is a) C₁₋₆ alkyl optionally substituted with one or more OH, halo, or —CN, b) —(CH₂)_(q)-aryl, or c) —(CH₂)_(q)—OR₄₂; R₄₂ is a) H, b) C₁₋₆ alkyl, c) —(CH₂)_(q)-aryl, or d) —C(═O)—C₁₋₆ alkyl; aryl is a) phenyl, b) pyridyl, or c) napthyl; a to c optionally substituted with one or more halo, —CN, OH, SH, C₁₋₆ alkyl, C₁₋₆ alkoxy, or C₁₋₆ alkylthio; h is 1, 2, or 3; i is 0, 1, or 2; j is 0 or 1, with the proviso that when j is 0, Y₂ is —CH₂—; k is 3, 4, or 5; l is 2 or 3; m is 4 or 5; n is 0, 1, 2, 3, 4, or 5; p is 0, 1, 2, 3, 4, or 5; with the proviso that n and p together are 1, 2, 3, 4, or 5; q is 1, 2, 3, or 4; u is 1 or 2; w is 0, 1, 2, or 3; x is 0, 1, 2, 3 or 4; and y is 0, 1, 2, 3 or 4; with the proviso that x and y taken together are 3 or 4; z is 1, 2, 3, 4 or 5, provided that i and z taken together are 2, 3, 4 or 5; and G is


2. The oxazolidinone derivative of claim 1, wherein said derivative is a compound of Formula (VIII)

wherein R is —CH₂-G-A.
 3. An oxazolidinone derivative of formula (XIII)

wherein R is -G-A; J is O or S; R₁′ is a) H, b) OH, c) alkyl, d) alkoxy, e) alkenyl, f) amino, g) substituted alkyl, h) substituted alkoxy, i) substituted alkenyl, or j) substituted amino;

R₂₁₀ is

R₃₁₀, R₄₁₀ and R₅₁₀ each independently are a) H, b) C₁₋₄ alkyl, c) halogen, d) C₁₋₄ alkoxy, e) hydroxy, f) (CH₂)OP(O)(OH)₂, g) C₁₋₄ acyloxy, or h) C₁₋₄ alkyl substituted by halogen, hydroxy, acyloxy, NP₁₂₁₀R₁₃₁₀, or alkoxy; and R₆₁₀ is a) H, b) CH₃, or c) C₂H₅; A is

R₄ is a) C₁₋₄ alkyl optionally substituted with one or more halos, OH, CN, NR₁₀R₁₁ or —CO₂R₁₃, b) C₂₋₄ alkenyl, c) —NR₁₆R₁₈, d) —N₃, e) —NHC(═O)R₇, f) —NR₂₀C(═O)R₇, g) —N(R₁)₂, h) —NR₁₆R₁₉, or i) —NR₁₉R₂₀, R₅ and R₆ at each occurrence are the same or different and are a) C₁₋₂ alkyl, or b) R₅ and R₆ taken together are —(CH₂)_(k)—; R₇ is C₁₋₄ alkyl optionally substituted with one or more halos; R₁₀ and R₁₁ at each occurrence are the same or different and are a) H, b) C₁₋₄ alkyl, or c) C₃₋₈ cycloalkyl; R₁₃ is a) H, or b) C₁₋₄ alkyl; R₁₄ and R₁₅ at each occurrence are the same or different and are a) C₁₋₄ alkyl, or b) R₁₄ and R₁₅ taken together are —(CH)_(l)—; R₁₆ is a) H, b) C₁₋₄ alkyl, or c) C₃₋₈ cycloalkyl; R₁₇ is a) C₁₋₄ alkyl, or b) C₃₋₈ cycloalkyl; R₁₈ is a) H, b) C₁₋₄ alkyl, c) C₂₋₄ alkenyl, d) C₃₋₄ cycloalkyl, e) —OR₁₃ or f) —NR₂₁R₂₂; R₁₉ is a) Cl, b) Br, or c) I; R₂₀ is a physiologically acceptable cation; R₂₁ and R₂₂ at each occurrence are the same or different and are a) H, b) C₁₋₄ alkyl, or c) —NR₂₁R₂₂ taken together are —(CH₂)_(m)—; wherein R₂₃ and R₂₄ at each occurrence are the same or different and are a) H, b) F, c) Cl, d) C₁₋₂ alkyl, e) CN f) OH, g) C₁₋₂ alkoxy, h) nitro, or i) amino; Q is

m) a diazinyl group optionally substituted with X and Y, n) a triazinyl group optionally substituted with X and Y, o) a quinolinyl group optionally substituted with X and Y, p) a quinoxalinyl group optionally substituted with X and Y, q) a naphthyridinyl group optionally substituted with X and Y,

Q and R₂₄ taken together are

wherein Z¹ is a) —CH₂—, b) —CH(R¹⁰⁴)—CH₂₋₇ c) —C(O)—, or d) —CH₂CH₂CH₂—; wherein Z² is a) —O₂S—, b) —O—, c) —N(R¹⁰⁷)—, d) —OS—, e) —S—, or f) S(O)(NR₁₉₀) wherein Z³ is a) —O₂S—, b) —O—, c) —OS—, d) —S—, or e) S(O)(NR₁₉₀) wherein A¹ is a) H—, or b) CH₃; wherein A² is a) H—, b) HO—, c) CH₃—, d) CH₃O—, e) R¹⁰²O—CH₂—C(O)—NH— f) R¹⁰³O—C(O)—NH—, g) (C₁-C₂)alkyl-O—C(O)—, h) HO—CH₂—, i) CH₃O—NH—, j) (C₁-C₃)alkyl-O₂C— k) CH₃—C(O)—, l) CH₃—C(O)—CH₂—,

A¹ and A² taken together are:

wherein R¹⁰² is a) H—, b) CH₃—, c) phenyl-CH₂—, or d) CH₃C(O)—; wherein R¹⁰³ is a) (C₁-C₃)alkyl-, or b) phenyl-; wherein R¹⁰⁴ is a) H—, or b) HO—; wherein R¹⁰⁶ is a) CH₃—C(O)—, b) H—C(O)—, c) Cl₂CH—C(O)—, d) HOCH₂—C(O)—, e) CH₃SO₂—,

g) F2CHC(O)—,

i) H₃C—C(O)—O—CH₂—C(O)—, j) H—C(O)—O—CH₂—C(O)—,

l) HC≡C—CH₂O—CH₂—C(O)—, or m) phenyl-CH₂—O—CH₂—C(O)—; wherein R¹⁰⁷ is a) R¹⁰²O—C(R¹¹⁰)(R¹¹¹)—C(O)— b) R¹⁰³O—C(O)—, c) R¹⁰⁸—C(O)—,

f) H₃C—C(O)—(CH₂)₂—C(O)—, g) R¹⁰⁹—SO₂—,

i) HO—CH₂—C(O)—, j) R¹¹⁶—(CH₂)₂—, k) R¹¹³—C(O)—O—CH—C(O)—, l) (CH₃)₂N—CH₂—C(O)—NH—, m) NC—CH₂—, n) F₂—CH—CH₂—, or o) R⁵⁰R¹⁵¹NSO₂ p) C(O)CR₁₈₀R₁₈₀R₁₈₁OR₈₈₂, q) C(O)CH₂S(O)_(l)CH₃, r) C(O)CH₂S(O)(NR₁₈₃)CH₃, s) C(S)R₁₈₄, t) C(O)CH₂OR₁₈₈, u) C(O)(CH₂)_(j)C(O)CH₃, v) C(O)(CH₂OH)₂CH₃, w) C(O)CH₂CH₂OR₁₃₉, or x) —CN; wherein R¹⁰⁸ is a) H—, b) (C₁-C₄)alkyl, c) aryl —(CH₂)P, d) ClH₂C—, e) Cl₂HC—, f) FH₂C—, g) F2HC—, h) (C₃-C₆) cycloalkyl, or i) CNCH₂—. wherein R¹⁰⁹ is a) alkylC₁-C₄, b) —CH₂Cl c) —CH₂CH═CH₂, d) aryl, or e) —CH₂CN; wherein R¹¹⁰ and R¹¹¹ are independently a) H—, b) CH₃—; or wherein R¹¹² is a) H—, b) CH₃O—CH₂O—CH₂—, or c) HOCH₂—; wherein R¹¹³ is a) CH₃—, b) HOCH₂—, c) (CH₃)₂N-phenyl, or d) (CH₃)₂N—CH₂—; wherein R¹¹⁴ is a) HO—, b) CH₃O—, c) H₂N—, d) CH₃O—C(O)—O—, e) CH₃—C(O)—O—CH₂—C(O)—O—, f) phenyl-CH₂—O—CH₂—C(O)O—, g) HO—(CH₂)₂—O—, h) CH₃O—CH₂—O—(CH₂)₂—O—, or i) CH₃O—CH₂—O—; wherein R¹¹⁵ is a) H—, or b) Cl—; wherein R¹¹⁶ is a) HO— b) CH₃O—, or c) F; wherein R¹⁵⁰ and R¹⁵¹ are each H or alkyl C₁-C₄ or R¹⁵⁰ and R¹⁵¹ taken together with the nitrogen atom to which each is attached form a monocyclic heterocyclic ring having from 3 to 6 carbon atoms; R₁₅₂ is a) H, b) C₁₋₄alkyl, c) C₁₋₄heteroalkyl, d) (CH₂)_(l)C(═O)OC₁₋₄alkyl, e) (CH₂)_(i)C(═O)C₁₋₄alkyl, f) aryl, or g) het¹; R¹⁵³ and P₁₅₄ are independently a) H, b) F, c) C₁₋₄alkyl, d) C₃₋₆cycloalkyl, e) C₁₋₄heteroalkyl, f) aryl, g) het¹, h) OC₁₋₄alkyl, i) O(C═O)C₁₋₄alkyl, j) (C═O)OC₁₋₄alkyl; or k) R₁₅₃ and R₁₅₄ taken together are C₃₋₆cycloalkyl; R₁₅₅ is a) H, b) F, c) C₁₋₄alkyl, d) OC₁₋₄alkyl, e) SC₁₋₄alkyl, or f) NHC₁₋₄alkyl; R₁₅₆ is a) H, b) C₁₋₄alkyl, c) OC₁₋₄alkyl, d) SC₁₋₄alkyl, or e) NHC₁₋₄alkyl; R₁₅₇ is a) —H, b) —F, c) —Cl, d) —NH₂, e) —OH, f) —CN, g) —C₁₋₄alkyl, h) —OC₁₋₄alkyl, i) —C₁₋₄alkyl-W—C₁₋₄alkyl, j) —NHC₁₋₄alkyl, k) —(CH₂)_(i)C₃₋₆cycloalkyl, l) —C(═O)C₁₋₄alkyl, m) —OC(═O)C₁₋₄alkyl, n) —C(═O)OC₁₋₄alkyl, o) —S(O)_(i)C₁₋₄alkyl, or p) —C(═O)NHC₁₋₄alkyl; R₁₅₈ is a) —H, b) —CH₃, c) —F, or d) —OH; R₁₅₉ is a) —H, b) —C₁₋₄alkyl, c) —C(═O)C₁₋₄alkyl, d) —C(═O)NHC₁₋₄alkyl, e) —OC(═O)C₁₋₄alkyl, f) —C(═O)OC₁₋₄alkyl, or g) —S(O)_(i)C₁₋₄alkyl, or h) —C₁₋₄alkyl-W₁—C₁₋₄alkyl; R₁₆₀ is H, C₂₋₆ alkenyl, C₂₋₇alkynyl, C₁₋₆ alkyl substituted with one or two of the following: a) F, b) Cl, c) CF₃, d) —OH, e) C₁₋₄alkoxy, f) —CH₂C(═O)C₁₋₄alkyl, g) —OC(═O)N(R₆₁)₂, h) C₁₋₄alkyl S(°)_(n), (wherein n is 0, 1 or 2), i) —CN, j) carboxy, k) —C₁₋₄alkoxycarbonyl, l) —C(═O)N(R₁₆₁)₂, m) —N(R₁₆₁)SO₂C₁₋₄ alkyl, n) —N(R₁₆₁)C(═O)C₁₋₄ alkyl, o) —N(R₁₆₁)C(═O)N(R₄)₂, p) —N(R₁₆₁)C(═O)C₁₋₄ alkoxy, q) aryl, or r) Het₁; R₁₆₁ is a) H, or b) C₁₋₃ alkyl; R₁₆₂ is a) H, b) C₁₋₈ alkyl, optionally substituted with one to three F, Cl, OH, CN, NH₂, OC(═O)C₁₋₄alkyl, or OC₁₋₄ alkyl, c) C₃₋₈ alkene, or d) C(═O)NR₁₆₃R₁₆₄; R₁₆₃ and R₁₆₄ are independently a) H, or b) C₁₋₈ alkyl, optionally substituted with one to three F, Cl, OH, CN, or NH₂; R₁₆₅ is C₁₋₄ alkyl, optionally substituted with 1-3 R₁₆₈; R₁₆₆ is a) C₁₋₈ alkyl, optionally substituted with 1-3 halo, CN, NO₂, OH, SH or NH₂, b) —C(═O)R₁₆₇ or c) —C(═S)NHC₁₋₄ alkyl; R₁₆₇ is a) H, b) C₁₋₆ alkyl, optionally substituted with OH, C₁₋₄ alkoxy, NH₂, SH or halo, or c) —CH₂OC(═O)C₁₋₄ alkyl; R₁₆₈ is j) halo, k) —CN, l) —OH, m) —SH, n) —NH₂, o) —OR₁₆₉, p) —NHR₁₆₉, q) —N(R₁₆₉)₂, or r) —S(═O)_(i)R₁₆₉; R₁₆₉ is g) C₁₋₆ alkyl, h) —C(═O)C₁₋₄ alkyl, i) —C(═O)O C₁₋₄ alkyl, j) —C(═O)NH₂, k) —C(═O)NH C₁₋₄ alkyl, or l) —SO₂C₁₋₄ alkyl; with the proviso that where j is 0, Y₂ is —CH₂—. R₁₇₀ is a) H, b) C₁₋₁₂ alkyl, optionally substituted with phenyl or CN, or c) C₂₋₁₂ alkyl substituted with OH, SH, NH₂, —OC₁₋₆ alkyl, —NHC₁₋₆ alkyl, —NHCOC₁₋₆ alkyl, —NHSO₂C₁₋₁₆ alkyl, —S(O)_(i)C₁₋₆ alkyl, or one to three halo; R₁₇₂ is a) H, b) C₁₋₈ alkyl, c) aryl, d) het₁, e) C(═W)R₁₇₄, f) C(═O)OR₁₇₅, or g) S(═O)_(i)R₁₇₆; R₁₇₃ is a) H, or b) C₁₋₈ alkyl; R₁₇₄ is a) H, b) aryl, c) het₁, d) NR₁₇₇R₁₇₈, or e) C₁₋₈ alkyl; R₁₇₅ is a) C₁₋₈ alkyl, b) aryl, or c) het₁; R₁₇₆ is a) aryl, b) het₁, c) NR₁₇₇R₁₇₈, or d) C₁₋₈ alkyl; R₁₇₇ and R₁₇₈ are independently a) H, b) C₁₋₈ alkyl, or c) aryl; R₁₈₀ and R₁₈₁ taken together form C₃₋₅ cycloalkyl; R₁₈₂ is H, CH₃ or C₁₋₄ alkanoyl; R₁₈₃ is H, C₁₋₄ alkyl, C₁₋₄ alkanoyl, —C(═O)NH—C₁₋₄ alkyl or —CO₂C₁₋₄ alkyl; R₁₈₄ is C₁₋₄ alkyl, CH₂OR₁₈₆, S—C₁₋₄ alkyl, OC₁₋₄ alkyl, or NR₁₈₇R₁₈₈; R₁₈₅ is phenyl, —CO₂—(CH₂)₂—OCH₃, —P(═O)(OH)₂, —C(═O)—NR₁₈₇R₁₈₆, or —C(═O)—(CH₂)₂—CO₂H; R₁₈₆ is H, phenyl, benzyl, CH₃ or C(═O)CH₃; R₁₈₇ and R₁₈₈ are independently H or C₁₋₃ alkyl; or R₁₈₇ and R₁₈₈ taken together form a 5- or 6-membered saturated heterocycle, wherein said saturated heterocycle may further contain one or two additional hetero-atoms selected from a group consisting of O, S(O)_(n) or NR₁₈₂; R₁₈₉ is H, CH₃ or benzyl; R¹⁹⁰ is a) H, b) C₁₋₄ alkyl, c) C(═O)C₁₋₄ alkyl, d) C(═O)OC₁₋₄ alkyl, e) C(═O)NHR₁₉₁, or f) C(═S)NHR₁₉₁; R₁₉₁ is H, C₁₋₄ alkyl, or phenyl; at each occurrence, alkyl in R₁₉₀ and R₁₉₁ is optionally substituted with one or more halo, CN, NO₂, phenyl, C₃₋₆ cycloalkyl, OR₁₉₂, C(═O)R₁₉₂, OC(═O)R₁₉₂, C(═O)OR₁₉₂, SC(═O)_(i)R₁₉₂, S(═O)_(i)NR192R₁₉₂, NR₁₉₂R₁₉₂, NR₁₉₂SO₂R₁₉₂, NR₁₉₂SO₂R₁₉₂R₁₉₂, NR₁₉₂C(═O)R₁₉₂, C(═O)NR₁₉₂R₁₉₂, NR₁₉₂R₁₉₂, oxo or oxime; R₁₉₂ is H, C₁₋₄ alkyl, or phenyl; at each occurrence, phenyl in R₁₉₁ and R₁₉₂ is optionally substituted with one or more halo, CN, NO₂, phenyl, C₃₋₆ cycloalkyl, OR₁₉₂, C(═O)R₁₉₂, OC(═O)R₁₉₂, C(═O)OR₁₉₂, S(═O)_(l)R₁₉₆, S(═O)_(i)NR₁₉₂R₁₉₂, NR₁₉₂SO₂R₁₉₂, NR₁₉₂SO₂NR₁₉₂R₁₉₂, NR₁₉₂C(═O)R₁₉₂, C(═O)NR₁₉₂R₁₉₂, or NR₁₉₂R₁₉₂; R₁₉₃ is selected from the group consisting of null, H, C₁-C₄alkyl, C₃-C₅cycloalkyl, C₁-C₄haloalkyl, and halophenyl; R₁₉₄ is selected from the group consisting of H, alkyl, C₁-C₂alkoxy, halo, and haloalkoxy, or R₁₉₃ and R₁₉₄ can be taken together to form a 5- or 6-membered, optionally substituted, heteroalkyl or heteroaryl ring; R₁₉₅ is H or F; R₁₉₆ is selected from the group consisting of H, methyl, amino, and F; R₁₉₇ is H, CH₃, or F; B is an unsaturated 4-atom linker having one nitrogen and three carbons; M is a) H, b) C₁₋₈ alkyl, c) C₃₋₈ cycloalkyl, d) —(CH₂)_(m)OR₁₃, or e) —(CH₂)_(h)—NR₂₁R₂₂; Z is a) O, b) S, or c) NM; W is a) CH, b) N, or c) S or O when Z is NM; Y is a) H, b) F, c) Ci, d) Br, e) C₁₋₃ alkyl, or f) NO₂; X is a) H, b) —CN, c) OR₂₇, d) halo, e) NO₂, f) tetrazoyl, g) —SH, h) —S(═O)_(i)R₄, i) —S(═O)₂—N═S(O)_(j)R₅R₆, j) —SC(═O)R₇, k) —C(═O)R₂₅, l) —C(═O)NR₂₇R₂₈, m) —C(═NR₂₉)R₂₅, n) —C(R₂₅)(R₂₈)—OR₁₃, o) —C(R₂₅)(R₂₈)—OC(═O)R₁₃, p) —C(R₂₈)(OR₁₃)—(CH₂)_(h)—NR₂₇R₂₈, q) —NR₂₇R₂₈, r) —N(R₂₇)C(═O)R₇, s) —N(R₂₇)—S(═O)_(i)R₇, t) —C(OR₁₄)(OR₁₅)R₂₈, u) —C(R₂₅)(R₁₆)—NR₂₇R₂₆, or v) C₁₋₈ alkyl substituted with one or more halos, OH, ═O other than at alpha position, —S(═O)1R₁₇, —NR₂₇R₂₈, C₂₋₅ alkenyl, C₂₋₅ alkynyl, or C₃₋₈ cycloalkyl; X₁ is N or CR¹⁵⁸; Y₁ is a) S(O)i, b) S(NR₁₅₉), or c) S(NR₁₅₉)(O) W₁ is O or S; X₂ is O or NR₁₆₂; X₃ is S(O)_(i) or NR₁₆₆; Y₂ is a) O b) NH, c) CH₂, or d) S(O)_(i); X₄ is a) O b) NR₁₇₂, c) S(O)_(l), or d) S(O)(NR₁₇₃); and Y₃ is CH or N; R₄, R₅, R₆, R₇, R₁₃, R₁₄, R₁₅, R₁₆, and R₁₇ are the same as defined above; R₂₅ is a) H, b) C₁₋₈ alkyl optionally substituted with one or more halos, C₃₋₈ cycloalkyl, C₁₋₄ alkyl substituted with one or more of —S(═O)_(i)R₁₇, —OR₁₃, or OC(═O)R₁₃, NR₂₇R₂₈, or c) C₂₋₅ alkenyl optionally substituted with CHO, or CO₂R₁₃; R₂₆ is a) R₂₈, or b) NR₂₇NR₂₈; R₂₇ and R₂₈ at each occurrence are the same or different and are a) H, b) C₁₋₈ alkyl, c) C₃₋₈ cycloalkyl, d) —(CH₂)_(m)OR₁₃, e) —(CH₂)—NR₂₁R₂₂, or f) R₂₇ and R₂₈ taken together are —(CH₂)₂O(CH₂)₂—, —(CH₂)_(h)CH(COR₇)—, or —(CH₂)₂N(CH₂)₂(R₇) R₂₉ is a) —NR₂₇R₂₈, b) —OR₂₇, or c) —NHC(═O)R₂₈; wherein R₃₀ is a) H, b) C₁₋₈ alkyl optionally substituted with one or more halos, or c) C₁₋₈ alkyl optionally substituted with one or more OH, or C₁₋₆ alkoxy; wherein E is a) NR₃₉, b) —S(═O)_(l), c) O, or d) S(O)(NR₉₀) R₃₈ is a) H, b) C₁₋₆ alkyl, c) —(CH₂)_(q)-aryl, or d) halo; R₃₉ is a) H, b) C₁₋₆ alkyl optionally substituted with one or more OH, halo, or —CN, c) —(CH₂)_(q)-aryl, d) —CO₂R₄₀, e) —COR₄₁, f) —C(═O)—(CH₂)_(q)—C(═O)R₄₀, g) —S(═O)₂—C₁₋₆ alkyl, h) —S(═O)₂—(CH₂)_(q)-aryl, or i) —(C═O)_(j)-Het; R₄₀ is a) H, b) C₁₋₆ alkyl optionally substituted with one or more OH, halo, or —CN, c) —(CH₂)_(q)-aryl, or d) —(CH₂)_(q)—OR₄₂; R₄₁ is a) C₁₋₆ alkyl optionally substituted with one or more OH, halo, or —CN, b) —(CH₂)_(q)-aryl, or c) —(CH₂)_(q)—OR₄₂; R₄₂ is a) H, b) C₁₋₆ alkyl, c) —(CH₂)_(q)-aryl, or d) —C(═O)—C₁₋₆ alkyl; aryl is a) phenyl, b) pyridyl, or c) napthyl; a to c optionally substituted with one or more halo, —CN, OH, SH, C₁₋₆ alkyl, C₁₋₆ alkoxy, or C₁₋₆ alkylthio; h is 1, 2, or 3; i is 0, 1, or 2; j is 0 or 1, with the proviso that when j is 0, Y₂ is —CH₂—; k is 3, 4, or 5; l is 2 or 3; m is 4 or 5; n is 0, 1, 2, 3, 4, or 5; p is 0, 1, 2, 3, 4, or 5; with the proviso that n and p together are 1, 2, 3, 4, or 5; q is 1, 2, 3, or 4; u is 1 or 2; w is 0, 1, 2, or 3; x is 0, 1, 2, 3 or 4; and y is 0, 1, 2, 3 or 4; with the proviso that x and y taken together are 3 or 4; z is 1, 2, 3, 4 or 5, provided that i and z taken together are 2, 3, 4 or 5; and G is


4. The oxazolidinone derivative of claim 3, wherein J is O, Q′ is b), R₂₁₀ is b), R₃₁₀ is H, R₄₁₀ is CH₃, R₅₁₀ is H and R₆₁₀ is CH₃.
 5. The oxazolidinone derivative of claim 1, wherein J is O, G is

 and A is


6. The oxazolidinone derivative of claim 2, wherein J is O and R is


7. The oxazolidinone derivative of claim 3, wherein R is


8. The oxazolidinone derivative of claim 1, wherein R₂₃ and R₂₄ are each independently H or F and Q is selected from the group consisting of


9. The oxazolidinone derivative of claim 2, wherein R₂₃ and R₂₄ are each independently H or F and Q is selected from the group consisting of


10. The oxazolidinone derivative of claim 3, wherein R₂₃ and R₂₄ are each independently H or F and Q is selected from the group consisting of


11. The oxazolidinone derivative of claim 1, wherein said derivative is 2-{3-[Acetyl({(5S)-3-[4-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-3-fluorophenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl) amino]-1,1-dimethyl-3-oxopropyl}-3,5-dimethylphenyldihydrogen phosphate.
 12. The oxazolidinone derivative of claim 1, wherein Q is

Q and R₂₄ taken together are

wherein A² is a) H—, b) HO—, c) CH₃—, d) CH₃O—, e) R¹⁰²O—CH₂—C(O)—NH— f) R¹⁰³O—C(O)—NH—, g) (C₁-C₂)alkyl-O—C(O)—, h) HO—CH₂—, i) CH₃O—NH—, j) (C₁-C₃)alkyl-O₂C— k) CH₃—C(O)—, or l) CH₃—C(O)—CH₂—; wherein R¹⁰⁶ is a) CH₃—C(O)—, b) H—C(O)—, c) Cl₂CH—C(O)—, d) HOCH₂—C(O)—, e) CH₃SO₂—, g) F2CHC(O)—, i) H₃C—C(O)—O—CH₂—C(O)—, j) H—C(O)—O—CH₂—C(O)—, l) HC≡C—CH₂O—CH₂—C(O)—, or m) phenyl-CH₂—O—CH₂—C(O)—; wherein R¹⁰⁷ is a) R¹⁰²O—C(R¹¹⁰)(R¹¹¹)—C(O)—, b) R¹⁰³O—C(O)—, c) R¹⁰⁸—C(O)—, f) H₃C—C(O)—(CH₂)₂—C(O)—, g) R¹⁰⁹—SO₂—, i) HO—CH₂—C(O)—, j) R¹¹⁶—(CH₂)₂—, k) R¹¹³—C(O)—O—CH₂—C(O)—, l) (CH₃)₂N—CH₂—C(O)—NH—, m) NC—CH₂—, n) F₂—CH—CH₂—, or o) R¹⁵⁰R¹⁵¹NSO₂ p) C(O)CR₁₈₀R₁₈₀R₁₈₁OR₁₈₂, q) C(O)CH₂S(O)_(l)CH₃, r) C(O)CH₂S(O)(NR₁₈₃)CH₃, s) C(S)R₁₈₄, t) C(O)CH₂OR₁₈₅, u) C(O)(CH₂)_(j)C(O)CH₃, v) C(O)(CH₂OH)₂CH₃, w) C(O)CH₂CH₂OR₁₈₉, or x) —CN.
 13. The oxazolidinone derivative of claim 2, wherein Q is

Q and R₂₄ taken together are

wherein A² is a) H—, b) HO—, c) CH₃—, d) CH₃O—, e) R¹⁰²O—CH₂—C(O)—NH— f) R¹⁰³O—C(O)—NH—, g) (C₁-C₂)alkyl-O—C(O)—, h) HO—CH₂—, i) CH₃O—NH—, j) (C₁-C₃)alkyl-O₂C— k) CH₃—C(O)—, or l) CH₃—C(O)—CH₂—; wherein R¹⁰⁶ is a) CH₃—C(O)—, b) H—C(O)—, c) Cl₂CH—C(O)—, d) HOCH₂—C(O)—, e) CH₃SO₂—, g) F2CHC(O)—, i) H₃C—C(O)—O—CH₂—C(O)—, j) H—C(O)—O—CH₂—C(O)—, l) HC≡C—CH₂O—CH₂—C(O)—, or m) phenyl-CH₂—O—CH₂—C(O)— wherein R¹⁰⁷ is a) R¹⁰²O—C(R¹¹⁰)(R¹¹¹)—C(O)—, b) R¹⁰³O—C(O) c) R¹⁰⁸—C(O)—, f) H₃C—C(O)—(CH₂)₂—C(O)—, g) R¹⁰⁹—SO₂—, i) HO—CH₂—C(O)—, i) R¹¹⁶—(CH₂)₂—, k) R¹¹³—C(O)—O—CH₂—C(O)— l)(CH₃)₂N—CH₂—C(O)—NH—, m) NC—CH₂—, n) F₂—CH—CH₂—, or o) R¹⁵⁰R¹⁵¹NSO₂ p) C(O)CR₁₈₀R₁₈₀R₁₈₁OR₁₈₂, q) C(O)CH₂S(O)_(i)CH₃, r) C(O)CH₂S(O)(NR₁₈₃)CH₃, s) C(S)R₁₈₄, t) C(O)CH₂OR₁₈₅, u) C(O)(CH₂)_(j)C(O)CH₃, v) C(O)(CH₂OH)₂CH₃, w) C(O)CH₂CH₂OR₁₈₉, or x) —CN.
 14. The oxazolidinone derivative of claim 3, wherein Q is

Q and R₂₄ taken together are

wherein A² is a) H—, b) HO—, c) CH₃—, d) CH₃O—, e) R¹⁰²O—CH₂—C(O)—NH— f) R¹⁰³O—C(O)—NH—, g) (C₁-C₂)alkyl-O—C(O)—, h) HO—CH₂—, i) CH₃O—NH—, j) (C₁-C₃)alkyl-O₂C— k) CH₃—C(O)—, or l) CH₃—C(O)—CH₂—; wherein R¹⁰⁶ is a) CH₃—C(O)—, b) H—C(O)—, c) Cl₂CH—C(O)—, d) HOCH₂—C(O)—, e) CH₃SO₂—, g) F2CHC(O)—, i) H₃C—C(O)—O—CH₂—C(O)—, j) H—C(O)—O—CH₂—C(O)—, l) HC≡C—CH₂O—CH₂—C(O)—, or m) phenyl-CH₂—O—CH₂—C(O)—; wherein R¹⁰⁷ is a) R¹⁰²O—C(R¹¹⁰)(R¹¹¹)—C(O)—, b) R¹⁰³O—C(O)—, c) R¹⁰⁸—C(O)—, f) H₃C—C(O)—(CH₂)₂—C(O)—, g) R¹⁰⁹—SO₂—, i) HO—CH₂—C(O)—, j) R¹¹⁶—(CH₂)₂—, k) R¹¹³—C(O)—O—CH₂—C(O)—, l) (CH₃)₂N—CH₂—C(O)—NH—, m) NC—CH₂—, n) F₂—CH—CH₂—, or o) R¹⁵⁰R¹⁵¹NSO₂ p) C(O)CR₁₈₀R₁₈₀R₁₈₁OR₁₈₂, q) C(O)CH₂S(O)_(i)CH₃, r) C(O)CH₂S(O)(NR₁₈₃)CH₃, s) C(S)R₁₈₄, t) C(O)CH₂OR₁₈₅, u) C(O)(CH₂)_(j)C(O)CH₃, v) C(O)(CH₂OH)₂CH₃, w) C(O)CH₂CH₂OR₁₈₉, or x) —CN.
 15. A method of preparing an oxazolidinone derivative having an improved water solubility comprising the steps of providing an amide of formula (III)

reacting the amide with a compound of formula (XIV)

to form a compound of formula (XV)

and removing the protecting groups to form a compound of formula (VIII)

wherein J is O or S, R is —CH₂-G-A, R₁ is a) C₁₋₄ alkyl, b) C₂₋₄ alkenyl, c) OC₁₋₄ alkyl, d) C₃₋₆ cycloalkyl, e) C₁₋₄ alkyl substituted with 1-3F, 1-2Cl, CN, —COOC₁₋₄ alkyl or a C₃₋₆ cycloalkyl; or f) H Pr is a protecting group; G is

and A is

R₄ is a) C₁₋₄ alkyl optionally substituted with one or more halos, OH, CN, NR₁₀R₁₁, or —CO₂R₁₃, b) C₂₋₄ alkenyl, c) —NR₁₆R₁₈, d) —N₃, e) —NHC(═O)R₇, f) —NR₂₀C(═O)R₇, g) —N(R₁₉)₂, h) —NR₁₆R₁₉, or i) —NR₁₉R₂₀, R₅ and R₆ at each occurrence are the same or different and are a) C₁₋₂ alkyl, or b) R₅ and R₆ taken together are —(CH₂)_(k)—; R₇ is C₁₋₄ alkyl optionally substituted with one or more halos; R₁₀ and R₁₁ at each occurrence are the same or different and are a) H, b) C₁₋₄ alkyl, or c) C₃₋₈ cycloalkyl; R₁₃ is a) H, or b) C₁₋₄ alkyl; R₁₄ and R₁₅ at each occurrence are the same or different and are a) C₁₋₄ alkyl, or b) R₁₄ and R₁₅ taken together are —(CH)_(l)—; R₁₆ is a) H, b) C₁₋₄ alkyl, or c) C₃₋₈ cycloalkyl; R₁₇ is a) C₁₋₄ alkyl, or b) C₃₋₈ cycloalkyl; R₁₈ is a) H, b) C₁₋₄ alkyl, c) C₂₋₄ alkenyl, d) C₃₋₄ cycloalkyl, e) —OR₁₃ or f) —NR₂₁R₂₂; R₁₉ is a) Cl, b) Br, or c) I; R₂₀ is a physiologically acceptable cation; R₂₁ and R₂₂ at each occurrence are the same or different and are a) H, b) C₁₋₄ alkyl, or c) —NR₂₁R₂₂ taken together are —(CH₂)_(m)—; wherein R₂₃ and R₂₄ at each occurrence are the same or different and are a) H, b) F, c) Cl, d) C₁₋₂ alkyl, e) CN f) OH, g) C₁₋₂ alkoxy, h) nitro, or i) amino; Q is

m) a diazinyl group optionally substituted with X and Y, n) a triazinyl group optionally substituted with X and Y, o) a quinolinyl group optionally substituted with X and Y, p) a quinoxalinyl group optionally substituted with X and Y, q) a naphthyridinyl group optionally substituted with X and Y,

Q and R₂₄ taken together are

wherein Z¹ is a) —CH₂—, b) —CH(R¹⁰⁴)—CH₂—, c) —C(O)—, or d) —CH₂CH₂CH₂—; wherein Z² is a) —O₂S—, b) —O—, c) —N(R¹⁰⁷)—, d) —OS—, e) —S—, or f) S(O)(NR₁₉₀) wherein Z³ is a) —O₂S—, b) —O—, c) —OS—, d) —S—, or e) S(O)(NR₁₉₀) wherein A¹ is a) H—, or b) CH₃; wherein A² is a) H—, b) HO—, c) CH₃—, d) CH₃O—, e) R¹⁰²O—CH₂—C(O)—NH— f) R¹⁰³O—C(O)—NH—, g) (C₁-C₂)alkyl-O—C(O)—, h) HO—CH₂—, i) CH₃O—NH—, j) (C₁-C₃)alkyl-O₂C— k) CH₃—C(O)—, l) CH₃—C(O)—CH₂—,

A¹ and A² taken together are:

wherein R¹⁰² is a) H—, b) CH₃—, c) phenyl-CH₂—, or d) CH₃C(O)—; wherein R¹⁰³ is a) (C₁-C₃)alkyl-, or b) phenyl-; wherein R¹⁰⁴ is a) H—, or b) HO—; wherein R¹⁰⁶ is a) CH₃—C(O)—, b) H—C(O)—, c) Cl₂CH—C(O)—, d) HOCH₂—C(O)—, e) CH₃SO₂—,

g) F2CHC(O)—,

i) H₃C—C(O)—O—CH₂—C(O)—, j) H—C(O)—O—CH₂—C(O)—,

l) HC≡C—CH₂O—CH₂—C(O)—, or m) phenyl-CH₂—O—CH₂—C(O)—; wherein R¹⁰⁷ is a) R¹⁰²—C(R¹¹⁰)(R¹¹¹)—C(O)—, b) R¹⁰³O—C(O)—, c) R⁰⁸—C(O)—,

f) H₃C—C(O)—(CH₂)₂—C(O)—, g) R¹⁰⁹—SO₂—,

i) HO—CH₂—C(O)—, j) R¹¹⁶—(CH₂)₂—, k) R¹³—C(O)—O—CH₂—C(O)— l) (CH₃)₂N—CH₂—C(O)—NH—, m) NC—CH₂—, n) F₂—CH—CH₂—, or o)R¹⁵⁰R¹⁵¹NSO₂ p) C(O)CR₁₈₀R₁₈₀R₁₈₁OR₁₈₂, q) C(O)CH₂S(O)_(i)CH₃, r) C(O)CH₂S(O)(NR₁₈₃)CH₃, s) C(S)R₁₈₄, t) C(O)CH₂OR₁₈₅, u) C(O)(CH₂)_(j)C(O)CH₃, v) C(O)(CH₂OH)₂CH₃, w) C(O)CH₂CH₂OR₁₈₉, or x) —CN; wherein R¹⁰⁸ is a) H—, b) (C₁-C₄)alkyl, c) aryl —(CH₂)_(p), d) ClH₂C—, e) Cl₂HC—, f) FH₂C—, g) F₂HC—, h) (C₃-C₆)cycloalkyl, or i) CNCH₂—. wherein R¹⁰⁹ is a) alkylC₁-C₄, b) —CH₂Cl c) —CH₂CH═CH₂. d) aryl, or e) —CH₂CN; wherein R¹¹⁰ and R¹¹¹ are independently a) H—, b) CH₃—; or wherein R¹¹² is a) H—, b) CH₃O—CH₂O—CH₂—, or c) HOCH₂—; wherein R¹¹³ is a) CH₃—, b) HOCH₂—, c) (CH₃)₂N-phenyl, or d) (CH₃)₂N—CH₂—; wherein R¹¹⁴ is a) HO—, b) CH₃O—, c) H₂N—, d) CH₃O—C(O)—O—, e) CH₃—C(O)—O—CH₂—C(O)—O—, f) phenyl-CH₂—O—CH₂—C(O)—O—, g) HO—(CH₂)₂—O—, h) CH₃O—CH₂—O— (CH₂)₂—O—, or i) CH₃O—CH₂—O—; wherein R¹¹⁵ is a) H—, or b) Cl—; wherein R¹¹⁶ is a) HO— b) CH₃O—, or c) F; wherein R¹⁵⁰ and R¹⁵¹ are each H or alkyl C₁-C₄ or R¹⁵⁰ and R¹⁵¹ taken together with the nitrogen atom to which each is attached form a monocyclic heterocyclic ring having from 3 to 6 carbon atoms; R₁₅₂ is a) H, b) C₁₋₄alkyl, c) C₁₋₄heteroalkyl, d) (CH₂)_(i)C(═O)OC₁₋₄alkyl, e) (CH₂)_(i)C(═O)C₁₋₄alkyl, f) aryl, or g) het¹; R₁₅₃ and R₁₅₄ are independently a) H, b) F, c) C₁₋₄alkyl, d) C₃₋₆cycloalkyl, e) C₁₋₄heteroalkyl, f) aryl, g) het¹, h) OC₁₋₄alkyl, i) O(C═O)C₁₋₄alkyl, j) (C═O)OC₁₋₄alkyl; or k) R₁₅₃ and R₁₅₄ taken together are C₃₋₆cycloalkyl; R₁₅₅ is a) H, b) F, c) C₁₋₄alkyl, d) OC₁₋₄alkyl, e) SC₁₋₄alkyl, or f) NHC₁₋₄alkyl; R₁₅₆ is a) H, b) C₁₋₄alkyl, c) OC₁₋₄alkyl, d) SC₁₋₄alkyl, or e) NHC₁₋₄alkyl; R₁₅₇ is a) —H, b) —F, c) —Cl, d) —NH₂, e) —OH, f) —CN, g) —C₁₋₄alkyl, h) —OC₁₋₄alkyl, i) —C₁₋₄alkyl-W—C₁₋₄alkyl, j) —NHC₁₋₄alkyl, k) —(CH₂)_(l)C₃₋₆cycloalkyl, l) —C(═O)C₁₋₄alkyl, m) —OC(═O)C₁₋₄alkyl, n) —C(═O)OC₁₋₄alkyl, o) —S(O)C₁₋₄alkyl, or p) —C(═O)NHC₁₋₄alkyl; R₁₅₈ is a) —H, b) —CH₃, c) —F, or d) —OH; R₁₅₉ is a) —H, b) —C₁₋₄alkyl, c) —C(═O)C₁₋₄alkyl, d) —C(═O)NHC₁₋₄alkyl, e) —OC(═O)C₁₋₄alkyl, f) —C(═O)OC₁₋₄alkyl, or g) —S(O)_(i)C₁₋₄alkyl, or h) —C₁₋₄alkyl-W₁—C₁₋₄alkyl; R₁₆₀ is H, C₂₋₆ alkenyl, C₂₋₇alkynyl, C₁₋₆ alkyl substituted with one or two of the following: a) F, b) Cl, c) CF₃, d) —OH, e) C₁₋₄alkoxy, f) —CH₂C(═O)C₁₋₄alkyl, g) —OC(═O)N(R₁₆₁)₂, h) C₁₋₄alkyl S(O)_(n), (wherein n is 0, 1 or 2), i) —CN, j) carboxy, k) —C₁₋₄alkoxycarbonyl, l) —C(═O)N(R₁₆₁)₂, m) —N(R₁₆₁)SO₂C₁₋₄ alkyl, n) —N(R₁₆₁)C(═O)C₁₋₄ alkyl, o) —N(R₁₆₁)C(═O)N(R₄)₂, p) —N(R₁₆₁)C(═O)C₁₋₄ alkoxy, q) aryl, or r) Het₁; R₁₆₁ is a) H, or b) C₁₋₃ alkyl; R₁₆₂ is a) H, b) C₁₋₈ alkyl, optionally substituted with one to three F, Cl, OH, CN, NH₂, OC(═O)C₁₋₄alkyl, or OC₁₋₄ alkyl, c) C₃₋₈ alkene, or d) C(═O)NR₁₆₃R₁₆₄; R₁₆₃ and R₁₆₄ are independently a) H, or b) C₁₋₈ alkyl, optionally substituted with one to three F, Cl, OH, CN, or NH₂; R₁₆₅ is C₁₋₄ alkyl, optionally substituted with 1-3 R₁₆₈; R₁₆₆ is a) C₁₋₈ alkyl, optionally substituted with 1-3 halo, CN, NO₂, OH, SH or NH₂, b) —C(═O)R₁₆₇ or c) —C(═S)NHC₁₋₄ alkyl; R₁₆₇ is a) H, b) C₁₋₆ alkyl, optionally substituted with OH, C₁₋₄ alkoxy, NH₂, SH or halo, or c) —CH₂OC(═O)C₁₋₄ alkyl; R₁₆₈ is j) halo, k) —CN, l) —OH, m) —SH, n) —NH₂, o) —OR₁₆₉, p) —NHR₁₆₉, q) —N(R₁₆₉)₂, or r) —S(═O)_(i)R₁₆₉; R₁₆₉ is g) C₁₋₆ alkyl, h) —C(═O)C₁₋₄ alkyl, i) —C(═O)O C₁₋₄ alkyl, j) —C(═O)NH₂, k) —C(═O)NH C₁₋₄ alkyl, or l) —SO₂C₁₋₄ alkyl; with the proviso that where j is 0, Y₂ is —CH₂—. R₁₇₀ is a) H, b) C₁₋₁₂ alkyl, optionally substituted with phenyl or CN, or c) C₂₋₁₂ alkyl substituted with OH, SH, NH₂, —OC₁₋₆ alkyl, —NHC₁₋₆ alkyl, —NHCOC₁₋₆ alkyl, —NHSO₂C₁₋₆ alkyl, —S(O)_(i)C₁₋₆ alkyl, or one to three halo; R₁₇₂ is a) H, b) C₁₋₈ alkyl, c) aryl, d) het₁, e) C(═W)R₁₇₄, f) C(═O)OR₁₇₅, or g) S(═O)_(i)R₁₇₆; R₁₇₃ is a) H, or b) C₁₋₈ alkyl; R₁₇₄ is a) H, b) aryl, c) het₁, d) NR₁₇₇P₁₇₈, or e) C₁₋₈ alkyl; R₁₇₅ is a) C₁₋₈ alkyl, b) aryl, or c) het₁; R₁₇₆ is a) aryl, b) het₁, c) NR₁₇₇R₁₇₈, or d) C₁₋₈ alkyl; R₁₇₇ and R₁₇₈ are independently a) H, b) C₁₋₈ alkyl, or c) aryl; R₁₈₀ and R₁₈₁ taken together form C₃₋₅ cycloalkyl; R₁₈₂ is H, CH₃ or C₁₋₄ alkanoyl; R₁₈₃ is H, C₁₋₄ alkyl, C₁₋₄ alkanoyl, —C(═O)NH—C₁₋₄ alkyl or —CO₂C₁₋₄ alkyl; R₁₈₄ is C₁₋₄ alkyl, CH₂OR₁₈₆, S—C₁₋₄ alkyl, OC₁₋₄ alkyl, or NR₁₈₇R₁₈₈; R₁₈₅ is phenyl, —CO₂—(CH₂)₂—OCH₃, —P(═O)(OH)₂, —C(═O)—NR₁₈₇R₁₈₆, or —C(═O)—(CH₂)₂—CO₂H; R₁₈₆ is H, phenyl, benzyl, CH₃ or C(═O)CH₃; R₁₈₇ and R₁₈₈ are independently H or C₁₋₃ alkyl; or R₁₈₇ and R₁₈₈ taken together form a 5- or 6-membered saturated heterocycle, wherein said saturated heterocycle may further contain one or two additional hetero-atoms selected from a group consisting of O, S(O)_(n) or NR₁₈₂; R₁₈₉ is H, CH₃ or benzyl; a) H, b) C₁₋₄ alkyl, c) C(═O)C₁₋₄ alkyl, d) C(═O)OC₁₋₄ alkyl, e) C(═O)NHR₁₉₁, or f) C(═S)NHR₁₉₁; R₁₉₁ is H, C₁₋₄ alkyl, or phenyl; at each occurrence, alkyl in R₁₉₀ and R₁₉₁ is optionally substituted with one or more halo, CN, NO₂, phenyl, C₃₋₆ cycloalkyl, OR₁₉₂, C(═O)R₁₉₂, OC(═O)R₁₉₂, C(═O)OR₁₉₂, SC(═O)_(l)R₁₉₂, S(═O)_(l)NR₁₉₂R₁₉₂, NR₁₉₂R₁₉₂, NR₁₉₂SO₂R₁₉₂, NR₁₉₂SO₂R₁₉₂R₁₉₂, NR₁₉₂C(═O)R₁₉₂, C(═O)NR₁₉₂R₁₉₂, NR₁₉₂R₁₉₂, oxo or oxime; R₁₉₂ is H, C₁₋₄ alkyl, or phenyl; at each occurrence, phenyl in R₁₉₁ and R₁₉₂ is optionally substituted with one or more halo, CN, NO₂, phenyl, C₃₋₆ cycloalkyl, OR₁₉₂, C(═O)R₁₉₂, OC(═O)R₁₉₂, C(═O)OR₁₉₂, S(═O)_(i)R₁₉₆, S(═O)_(i)NR₁₉₂R₁₉₂, NR₁₉₂SO₂R₁₉₂, NR₁₉₂SO₂NR₁₉₂R₁₉₂, NR₁₉₂C(═O)R₁₉₂, C(═O)NR₁₉₂R₁₉₂, or NR₁₉₂R₁₉₂; R₁₉₃ is selected from the group consisting of null, H, C₁C₄alkyl, C₃-C₅cycloalkyl, C₁-C₄haloalkyl, and halophenyl; R₁₉₄ is selected from the group consisting of H, alkyl, C₁-C₂alkoxy, halo, and haloalkoxy, or R₁₉₃ and R₁₉₄ can be taken together to form a 5- or 6-membered, optionally substituted, heteroalkyl or heteroaryl ring; R₁₉₅ is H or F; R₁₉₆ is selected from the group consisting of H, methyl, amino, and F; R₁₉₇ is H, CH₃, or F; B is an unsaturated 4-atom linker having one nitrogen and three carbons; M is a) H, b) C₁₋₈ alkyl, c) C₃₋₈ cycloalkyl, d) —(CH₂)_(m)OR₁₃, or e) —(CH₂)_(h)—NR₂₁R₂₂; Z is a) O, b) S, or c) NM; W is a) CH, b) N, or c) S or O when Z is NM; Y is a) H, b) F, c) Cl, d) Br, e) C₁₋₃ alkyl, or f) NO₂; X is a) H, b) —CN, c) OR₂₇, d) halo, e) NO₂, f) tetrazoyl, g) —SH, h) —S(═O)_(i)R₄, i) —S(═O)₂—N═S(O)_(j)R₅R₆, j) —SC(═O)R₇, k) —C(═O)R₂₅, l) —C(═O)NR₂₇R₂₈, m) —C(═NR₂₉)R₂₅, n) —C(R₂₅)(R₂₈)—OR₁₃, o) —C(R₂₅)(R₂₈)—OC(═O)R₁₃, p) —C(R₂₈)(OR₁₃)—(CH₂)_(h)—NR₂₇R₂₈, q) —NR₂₇R₂₈, r) —N(R₂₇)C(═O)R₇, s) —N(R₂₇)—S(═O)_(i)R₇, t) —C(OR₁₄)(OR₁₅)R₂₈, u) —C(R₂₅)(R₁₆)—NR₂₇R₂₆, or v) C₁₋₈ alkyl substituted with one or more halos, OH, ═O other than at alpha position, —S(═O)_(l)R₁₇, —NR₂₇R₂₈, C₂₋₅ alkenyl, C₂₋₅ alkynyl, or C₃₋₈ cycloalkyl; X₁ is N or CR₁₅₈; Y₁ is a) S(O)i, b) S(NR₁₅₉), or c) S(NR₁₅₉)(O) W₁ is O or S; X₂ is O or NR₁₆₂; X₃ is S(O)_(l) or NR₁₆₆; Y₂ is a) O b) NH, c) CH₂, or d) S(O)_(i); X₄ is a) O b) NR₁₇₂, c) S(O)_(l), or d) S(O)(NR₁₇₃); and Y₃ is CH or N; R₄, R₅, R₆, R₇, R₁₃, R₁₄, R₁₅, R₁₆, and R₁₇ are the same as defined above; R₂₅ is a) H, b) C₁₋₈ alkyl optionally substituted with one or more halos, C₃₋₈ cycloalkyl, C₁₋₄ alkyl substituted with one or more of —S(═O)_(i)R₁₇, —OR₁₃, or OC(═O)R₁₃, NR₂₇R₂₈, or c) C₂₋₅ alkenyl optionally substituted with CHO, or CO₂R₁₃; R₂₆ is a) R₂₈, or b) NR₂₇NR₂₈; R₂₇ and R₂₈ at each occurrence are the same or different and are a) H, b) C₁₋₈ alkyl, c) C₃₋₈ cycloalkyl, d) —(CH₂)_(m)OR₁₃, e) —(CH₂)_(h)—NR₂₁R₂₂, or f) R₂₇ and R₂₈ taken together are —(CH₂)₂O(CH₂)₂—, —(CH₂)_(h)CH(COR₇)—, or —(CH₂)₂N(CH₂)₂(R₇); R₂₉ is a) —NR₂₇R₂₈, b) —OR₂₇, or c) —NHC(═O)R₂₈; wherein R₃₀ is a) H, b) C₁₋₈ alkyl optionally substituted with one or more halos, or c) C₁₋₈ alkyl optionally substituted with one or more OH, or C₁₋₆ alkoxy; wherein E is a) NR₃₉, b) —S(═O)_(i), c) O, or d) S(O)(NR₁₉₀) R₃₈ is a) H, b) C₁₋₆ alkyl, c) —(CH₂)_(q)-aryl, or d) halo; R₃₉ is a) H, b) C₁₋₆ alkyl optionally substituted with one or more OH, halo, or —CN, c) —(CH₂)_(q)-aryl, d) —CO₂R₄₀, e) —COR₄₁, f) —C(═O)—(CH₂)_(q)—C(═O)R₄₀, g) —S(═O)₂—C₁₋₆ alkyl, h) —S(═O)₂—(CH₂)_(q)-aryl, or i) —(C═O)_(j)-Het; R₄₀ is a) H, b) C₁₋₆ alkyl optionally substituted with one or more OH, halo, or —CN, c) —(CH₂)_(q)-aryl, or d) —(CH₂)_(q)—OR₄₂; R₄₁ is a) C₁₋₆ alkyl optionally substituted with one or more OH, halo, or —CN, b) —(CH₂)_(q)-aryl, or c) —(CH₂)_(q)—OR₄₂; R₄₂ is a) H, b) C₁₋₆ alkyl, c) —(CH₂)_(q)-aryl, or d) —C(═O)—C₁₋₆ alkyl; aryl is a) phenyl, b) pyridyl, or c) napthyl; a to c optionally substituted with one or more halo, —CN, OH, SH, C₁₋₆ alkyl, C₁₋₆ alkoxy, or C₁₋₆ alkylthio; h is 1, 2, or 3; i is 0, 1, or 2; j is 0 or 1, with the proviso that when j is 0, Y₂ is —CH₂—; k is 3, 4, or 5; l is 2 or 3; m is 4 or 5; n is 0, 1, 2, 3, 4, or 5; p is 0, 1, 2, 3, 4, or 5; with the proviso that n and p together are 1, 2, 3, 4, or 5; q is 1, 2, 3, or 4; u is 1 or 2; w is 0, 1, 2, or 3; x is 0, 1, 2, 3 or 4; and y is 0, 1, 2, 3 or 4; with the proviso that x and y taken together are 3 or 4; z is 1, 2, 3, 4 or 5, provided that i and z taken together are 2, 3, 4 or
 5. 16. The method of claim 15, wherein G is

 and A is


17. The method of claim 15, wherein the compound of formula (VIII) is 2-{3-[Acetyl({(5S)-3-[4-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-3-fluorophenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)amino]-1,1-dimethyl-3-oxopropyl}-3,5-dimethylphenyldihydrogen phosphate.
 18. A method of preparing an oxazolidinone derivative having an improved water solubility comprising the steps of providing an amide of formula (XVI)

reacting the amide with a compound of formula (XIV)

to form a compound of formula (XVII)

and removing the protecting groups to form a compound of formula (XVIII)

wherein J is O or S; R₁′ is a) H, b) OH, c) alkyl, d) alkoxy, e) alkenyl, f) amino; g) substituted alkyl, h) substituted alkoxy, i) substituted alkenyl, or j) substituted amino; Pr is a protecting group; R is -G-A; G is

and A is

R₄ is a) C₁₋₄ alkyl optionally substituted with one or more halos, OH, CN, NR₁₀R₁₁, or —CO₂R₁₃, b) C₂₋₄ alkenyl, c) —NR₁₆R₁₈, d) —N₃, e) —NHC(═O)R₇, f) —NR₂₀C(═O)R₇, g) —N(R₁₉)₂, h) —NR₁₆R₁₉, or i) —NR₁₉R₂0, R₅ and R₆ at each occurrence are the same or different and are a) C₁₋₂ alkyl, or b) R₅ and R₆ taken together are —(CH₂)_(k)—; R₇ is C₁₋₄ alkyl optionally substituted with one or more halos; R₁₀ and R₁₁ at each occurrence are the same or different and are a) H, b) C₁₋₄ alkyl, or c) C₃₋₈ cycloalkyl; R₁₃ is a) H, or b) C₁₋₄ alkyl; R₁₄ and R₁₅ at each occurrence are the same or different and are a) C₁₋₄ alkyl, or b) R₁₄ and R₁₅ taken together are —(CH)_(l)—; R₁₆ is a) H, b) C₁₋₄ alkyl, or c) C₃₋₈ cycloalkyl; R₁₇ is a) C₁₋₄ alkyl, or b) C₃₋₈ cycloalkyl; R₁₈ is a) H, b) C₁₋₄ alkyl, c) C₂₋₄ alkenyl, d) C₃₋₄ cycloalkyl, e) —OR₁₃ or f) —NR₂₁R₂₂; R₁₉ is a) Cl, b) Br, or c) I; R₂₀ is a physiologically acceptable cation; R₂₁ and R₂₂ at each occurrence are the same or different and are a) H, b) C₁₋₄ alkyl, or c) —NR₂₁R₂₂ taken together are —(CH₂)_(m)—; wherein R₂₃ and R₂₄ at each occurrence are the same or different and are a) H, b) F, c) Cl, d) C₁₋₂ alkyl, e) CN f) OH, g) C₁₋₂ alkoxy, h) nitro, or i) amino; Q is

m) a diazinyl group optionally substituted with X and Y, n) a triazinyl group optionally substituted with X and Y, o) a quinolinyl group optionally substituted with X and Y, p) a quinoxalinyl group optionally substituted with X and Y, q) a naphthyridinyl group optionally substituted with X and Y,

Q and R₂₄ taken together are

wherein Z¹ is a) —CH₂—, b) —CH(R¹⁰⁴)—CH₂—, c) —C(O)—, or d) —CH₂CH₂CH₂—; wherein Z² is a) —O₂S—, b) —O—, c) —N(R¹⁰⁷)—, d) —OS—, e) —S—, or f) S(O)(NR₁₉₀); wherein Z³ is a) —O₂S—, b) —O—, c) —OS—, d) —S—, or e) S(O)(NR₁₉₀) wherein A¹ is a) H—, or b) CH₃; wherein A² is a) H—, b) HO—, c) CH₃—, d) CH₃O—, e) R¹⁰²O—CH₂—C(O)—NH— f) R¹⁰³O—C(O)—NH—, g) (C₁-C₂)alkyl-O—C(O)—, h) HO—CH₂—, i) CH₃O—NH—, j) (C₁-C₃)alkyl-O₂C— k) CH₃—C(O)—, l) CH₃—C(O)—CH₂—,

A¹ and A² taken together are:

wherein R¹⁰² is a) H—, b) CH₃—, c) phenyl-CH₂—, or d) CH₃C(O)—; wherein R¹⁰³ is a) (C₁-C₃)alkyl-, or b) phenyl-; wherein R¹⁰⁴ is a) H—, or b) HO—; wherein R¹⁰⁶ is a) CH₃—C(O)—, b) H—C(O)—, c) Cl₂CH—C(O)—, d) HOCH₂—C(O)—, e) CH₃SO₂—,

g) F2CHC(O)—,

i) H₃C—C(O)—O—CH₂—C(O)—, j) H—C(O)—O—CH₂—C(O)—,

l) HC≡C—CH₂O—CH₂—C(O)—, or m) phenyl-CH₂—O—CH₂—C(O)—; wherein R¹⁰⁷ is a) R¹⁰²O—C(R¹¹⁰)(R¹¹¹) —C(O)—, b) R¹⁰³O—C(O)—, c) R¹⁰⁸—C(O)—,

f) H₃C—C(O)—(CH₂)₂—C(O)—, g) R¹⁰⁹—SO₂—,

i) HO—CH₂—C(O)—, j) R¹¹⁶—(CH₂)₂—, k) R¹¹³—C(O)—O—CH₂—C(O)— l) (CH₃)₂N—CH₂—C(O)—NH—, m) NC—CH₂—, n) F₂—CH—CH₂—, or o) R¹⁵⁰R¹⁵¹NSO₂ p) C(O)CR₁₈₀R₁₈₀R₁₈₁OR₁₈₂, q) C(O)CH₂S(O)_(i)CH₃, r) C(O)CH₂S(O)(NR₁₈₃)CH₃, s) C(S)R₁₈₄, t) C(O)CH₂OR₁₈₅, u) C(O)(CH₂)_(j)C(O)CH₃, v) C(O)(CH₂OH)₂CH₃, w) C(O)CH₂CH₂OR₁₈₉, or x) —CN; wherein R¹⁰⁸ is a) H—, b) (C₁-C₄)alkyl, c) aryl —(CH₂)_(p), d) CLH₂C—, e) Cl₂HC—, f) FH₂C—, g) F₂HC—, h) (C₃-C₆)cycloalkyl, or i) CNCH₂—, wherein R¹⁰⁹ is a) alkylC₁-C₄, b) —CH₂Cl c) —CH₂CH═CH₂, d) aryl, or e) —CH₂CN; wherein R¹¹⁰ and R¹¹¹ are independently a) H—, b) CH₃—; or wherein R¹¹² is a) H—, b) CH₃O—CH₂O—CH₂—, or c) HOCH₂—; wherein R¹¹³ is a) CH₃—, b) HOCH₂—, c) (CH₃)₂N-phenyl, or d) (CH₃)₂N—CH₂—; wherein R¹¹⁴ is a) HO—, b) CH₃O—, c) H₂N—, d) CH₃O—C(O)—O—, e) CH₃—C(O)—O—CH₂—C(O)—O—, f) phenyl-CH₂—O—CH₂—C(O)—O—, g) HO— (CH₂)₂—O—, h) CH₃O—CH₂—O— (CH₂)₂—O—, or i) CH₃O—CH₂—O—; wherein R¹¹⁵ is a) H—, or b) Cl—; wherein R¹¹⁶ is a) HO— b) CH₃O—, or c) F; wherein R¹⁵⁰ and R¹⁵¹ are each H or alkyl C₁-C₄ or R¹⁵⁰ and R¹⁵¹ taken together with the nitrogen atom to which each is attached form a monocyclic heterocyclic ring having from 3 to 6 carbon atoms; R₁₅₂ is a) H, b) C₁₋₄alkyl, c) C₁₋₄heteroalkyl, d) (CH₂)_(i)C(═O)OC₁₋₄alkyl, e) (CH₂)_(i)C(═O)C₁₋₄alkyl, f) aryl, or g) het¹; R₁₅₃ and R₁₅₄ are independently a) H, b) F, c) C₁₋₄alkyl, d) C₃₋₆cycloalkyl, e) C₁₋₄heteroalkyl, f) aryl, g) het¹, h) OC₁₋₄alkyl, i) O(C═O)C₁₋₄alkyl, j) (C═O)OC₁₋₄alkyl; or k) R₁₅₃ and R₁₅₄ taken together are C₃₋₆cycloalkyl; R₁₅₅ is a) H, b) F, c) C₁₋₄alkyl, d) OC₁₋₄alkyl, e) SC₁₋₄alkyl, or f) NHC₁₋₄alkyl; R₁₅₆ is a) H, b) C₁₋₄alkyl, c) OC₁₋₄alkyl, d) SC₁₋₄alkyl, or e) NHC₁₋₄alkyl; R₁₅₇ is a) —H, b) —F, c) —Cl, d) —NH₂, e) —OH, f) —CN, g) —C₁₋₄alkyl, h) —OC₁₋₄alkyl, i) —C₁₋₄alkyl-W—C₁₋₄alkyl, j) —NHC₁₋₄alkyl, k)—(CH₂)_(i)C₃₋₆cycloalkyl, l) —C(═O)C₁₋₄alkyl, m) —OC(═O)C₁₋₄alkyl, n) —C(═O)OC₁₋₄alkyl, o) —S(O)_(l)C₁₋₄alkyl, or p) —C(═O)NHC₁₋₄alkyl; R₁₅₈ is a) —H, b) —CH₃, c) —F, or d) —OH; R₁₅₉ is a) —H, b) —C₁₋₄alkyl, c) —C(═O)C₁₋₄alkyl, d) —C(═O)NHC₁₋₄alkyl, e) —OC(═O)C₁₋₄alkyl, f) —C(═O)OC₁₋₄alkyl, or g) —S(O)_(i)C₁₋₄alkyl, or h) —C₁₋₄alkyl-W₁—C₁₋₄alkyl; R₁₆₀ is H, C₂₋₆ alkenyl, C₂₋₇alkynyl, C₁₋₆ alkyl substituted with one or two of the following: a) F, b) Cl, c) CF₃, d) —OH, e) C₁₋₄alkoxy, f) —CH₂C(═O)C₁₋₄alkyl, g) —OC(═O)N(R₁₆₁)₂, h) C₁₋₄alkyl S(O)_(n), (wherein n is 0, 1 or 2), i) —CN, j) carboxy, k) —C₁₋₄alkoxycarbonyl, l) —C(═O)N(R₁₆₁)₂, m) —N(R₁₆₁)SO₂C₁₋₄ alkyl, n) —N(R₁₆₁)C(═O)C₁₋₄ alkyl, o) —N(R₁₆₁)C(═O)N(R₄)₂, p) —N(R₁₆₁)C(═O)C₁₋₄ alkoxy, q) aryl, or r) Het₁; R₁₆₁ is a) H, or b) C₁₋₃ alkyl; R₁₆₂ is a) H, b) C₁₋₈ alkyl, optionally substituted with one to three F, Cl, OH, CN, NH₂, OC(═O)C₁₋₄alkyl, or OC₁₋₄ alkyl, c) C₃₋₈ alkene, or d) C(═O)NR₁₆₃R₁₆₄; R₁₆₃ and R₁₆₄ are independently a) H, or b) C₁₋₈ alkyl, optionally substituted with one to three F, Cl, OH, CN, or NH₂; R₁₆₅ is C₁₋₄ alkyl, optionally substituted with 1-3 R₁₆₈; R₁₆₆ is a) C₁₋₈ alkyl, optionally substituted with 1-3 halo, CN, NO₂, OH, SH or NH₂, b) —C(═O)R₁₆₇ or c) —C(═S)NHC₁₋₄ alkyl; R₁₆₇ is a) H, b) C₁₋₆ alkyl, optionally substituted with OH, C₁₋₄ alkoxy, NH₂, SH or halo, or c) —CH₂OC(═O)C₁₋₄ alkyl; R₁₆₈ is j) halo, k) —CN, l) —OH, m) —SH, n) —NH₂, o) —OR₁₆₉, p) —NHR₁₆₉, q) —N(R₁₆₉)₂, or r) —S(═O)_(i)R₁₆₉; R¹⁶⁹ is g) C₁₋₆ alkyl, h) —C(═O)C₁₋₄ alkyl, i) —C(═O)O C₁₋₄ alkyl, j) —C(═O)NH₂, k) —C(═O)NH C₁₋₄ alkyl, or l) —SO₂C₁₋₄ alkyl; with the proviso that where j is 0, Y₂ is —CH₂—. R₁₇₀ is a) H, b) C₁₋₁₂ alkyl, optionally substituted with phenyl or CN, or c) C₂₋₁₂ alkyl substituted with OH, SH, NH₂, —OC₁₋₆ alkyl, —NHC₁₋₆ alkyl, —NHCOC₁₋₆ alkyl, —NHSO₂C₁₋₆ alkyl, —S(O)_(i)C₁₋₆ alkyl, or one to three halo; R₁₇₂ is a) H, b) C₁₋₈ alkyl, c) aryl, d) het₁, e) C(═W)R₁₇₄, f) C(═O)OR₁₇₅, or g) S(═O)_(i)R₁₇₆; R₁₇₃ is a) H, or b) C₁₋₈ alkyl; R₁₇₄ is a) H, b) aryl, c) het₁, d) NR₁₇₇R₁₇₈ or e) C₁₋₈ alkyl; R₁₇₅ is a) C₁₋₈ alkyl, b) aryl, or c) het₁; R₁₇₆ is a) aryl, b) het₁, c) NR₁₇₇R₁₇₈, or d) C₁₋₈ alkyl; R₁₇₇ and R₁₇₈ are independently a) H, b) C₁₋₈ alkyl, or c) aryl; R₁₈₀ and R₁₈₁ taken together form C₃₋₅ cycloalkyl; R₁₈₂ is H, CH₃ or C₁₋₄ alkanoyl; R₁₈₃ is H. C₁₋₄ alkyl, C₁₋₄ alkanoyl, —C(═O)NH—C₁₋₄ alkyl or —CO₂C₁₋₄ alkyl; R₁₈₄ is C₁₋₄ alkyl, CH₂OR₁₈₆, S—C₁₋₄ alkyl, OC₁₋₄ alkyl, or NR₁₈₇R₁₈₈; R₁₈₅ is phenyl, —CO₂—(CH₂)₂—OCH₃, —P(═O)(OH)₂, —C(═O)—NR₁₈₇R₁₈₆, or —C(═O)—(CH₂)₂—CO₂H; R₁₈₆ is H, phenyl, benzyl, CH₃ or C(═O)CH₃; R₁₈₇ and R₁₈₈ are independently H or C₁₋₃ alkyl; or R₁₈₇ and R₁₈₈ taken together form a 5- or 6-membered saturated heterocycle, wherein said saturated heterocycle may further contain one or two additional hetero-atoms selected from a group consisting of O, S(O)_(n) or NR₁₈₂; R₁₈₉ is H, CH₃ or benzyl; R₁₉₀ is a) H, b) C₁₋₄ alkyl, c) C(═O)C₁₋₄ alkyl, d) C(═O)OC₁₋₄ alkyl, e) C(═O)NHR₁₉₁, or f) C(═S)NHR₁₉₁; R₁₉₁ is H, C₁₋₄ alkyl, or phenyl; at each occurrence, alkyl in R₁₉₀ and R₁₉₁ is optionally substituted with one or more halo, CN, NO₂, phenyl, C₃₋₆ cycloalkyl, OR₁₉₂, C(═O)R₁₉₂, OC(═O)R₁₉₂, C(═O)OR₁₉₂, SC(═O)_(i)R₁₉₂, S(═O)_(i)NR₁₉₂R₁₉₂, NR₁₉₂R₁₉₂, NR₁₉₂SO₂R₁₉₂, NR₁₉₂SO₂R₁₉₂R₁₉₂, NR₁₉₂C(═O)R₁₉₂, C(═O)NR₁₉₂R₁₉₂, NR₁₉₂R₁₉₂, oxo or oxime; R₁₉₂ is H, C₁₋₄ alkyl, or phenyl; at each occurrence, phenyl in R₁₉₁ and R₁₉₂ is optionally substituted with one or more halo, CN, NO₂, phenyl, C₃₋₆ cycloalkyl, OR₁₉₂, C(═O)R₁₉₂, OC(═O)R₁₉₂, C(═O)OR₁₉₂, S(═O)_(i)R₁₉₆, S(═O)_(l)NR₁₉₂R₁₉₂, NR₁₉₂SO₂R₁₉₂, NR₁₉₂SO₂NR₁₉₂R₁₉₂, NR₁₉₂C(═O)R₁₉₂, C(═O)NR₁₉₂R₁₉₂, or NR₁₉₂R₁₉₂; R₁₉₃ is selected from the group consisting of null, H, C₁-C₄alkyl, C₃-C₅cycloalkyl, C₁-C₄haloalkyl, and halophenyl; R₁₉₄ is selected from the group consisting of H, alkyl, C₁-C₂alkoxy, halo, and haloalkoxy, or R₁₉₃ and R₁₉₄ can be taken together to form a 5- or 6-membered, optionally substituted, heteroalkyl or heteroaryl ring; R₁₉₅ is H or F; R₁₉₆ is selected from the group consisting of H, methyl, amino, and F; R₁₉₇ is H, CH₃, or F; B is an unsaturated 4-atom linker having one nitrogen and three carbons; M is a) H, b) C₁₋₈ alkyl, c) C₃₋₈ cycloalkyl, d) —(CH₂)OR₁₃, or e) —(CH₂)_(h)—NR₂₁R₂₂; Z is a) O, b) S, or c) NM; W is a) CH, b) N, or c) S or O when Z is NM; Y is a) H, b) F, c) Cl, d) Br, e) C₁₋₃ alkyl, or f) NO₂; X is a) H, b) —CN, c) OR₂₇, d) halo, e) NO₂, f) tetrazoyl, g) —SH, h) —S(═O)_(i)R₄, i) —S(═O)₂—N═S(O)_(j)R₅R₆, j) —SC(═O)R₇, k) —C(═O)R₂₅, l) —C(═O)NR₂₇R₂₈, m) —C(═NR₂₉)R₂₅, n) —C(R₂₅)(R₂₈)—OR₁₃, o) —C(R₂₅)(R₂₈)—OC(═O)R₁₃, p) —C(R₂₈)(OR₁₃)—(CH₂)_(h)—NR₂₇R₂₈, q) —NR₂₇R₂₈, r) —N(R₂₇)C(═O)R₇, s) —N(R₂₇)—S(═O)_(i)R₇, t) —C(OR₁₄)(OR₁₅)R₂₈, u) —C(R₂₅)(R₁₆)—NR₂₇R₂₆, or v) C₁₋₈ alkyl substituted with one or more halos, OH, ═O other than at alpha position, —S(═O)_(l)R₁₇, —NR₂₇R₂₈, C₂₋₅ alkenyl, C₂₋₅ alkynyl, or C₃₋₈ cycloalkyl; X₁ is N or CR₁₅₈; Y₁ is a) S(O)i, b) S(NR₁₅₉), or c) S(NR₁₅₉)(O); W₁ is O or S; X₂ is O or NR₁₆₂; X₃ is S(O)_(l) or NR₁₆₆; Y₂ is a) O b) NH, c) CH₂, or d) S(O)_(l); X₄ is a) O b) NR₁₇₂, c) S(O)_(i), or d) S(O)(NR₁₇₃); and Y₃ is CH or N; R₄, R₅, R₆, R₇, R₁₃, R₁₄, R₁₅, R₁₆, and R₁₇ are the same as defined above; R₂₅ is a) H, b) C₁₋₈ alkyl optionally substituted with one or more halos, C₃₋₈ cycloalkyl, C₁₋₄ alkyl substituted with one or more of —S(═O)_(i)R₁₇, —OR₁₃, or OC(═O)R₁₃, NR₂₇R₂₈, or c) C₂₋₅ alkenyl optionally substituted with CHO, or CO₂R₁₃; R₂₆ is a) R₂₈, or b) NR₂₇NR₂₈; R₂₇ and R₂₈ at each occurrence are the same or different and are a) H, b) C₁₋₈ alkyl, c) C₃₋₈ cycloalkyl, d) —(CH₂)_(m)OR₁₃, e) —(CH₂)_(h)—NR₂₁R₂₂, or f) R₂₇ and R₂₈ taken together are —(CH₂)₂O(CH₂)₂—, (CH₂)_(h)CH(COR₇)—, or —(CH₂)₂N(CH₂)₂(R₇); R₂₉ is a) —NR₂₇R₂₈, b) —OR₂₇, or c) —NHC(═O)R₂₈; wherein R₃₀ is a) H, b) C₁₋₈ alkyl optionally substituted with one or more halos, or c) C₁₋₈ alkyl optionally substituted with one or more OH, or C₁₋₆ alkoxy; wherein E is a) NR₃₉, b) —S(═O)_(i), c) O, or d) S(O)(NR₁₉₀); R₃₈ is a) H, b) C₁₋₆ alkyl, c) —(CH₂)_(q)-aryl, or d) halo; R₃₉ is a) H, b) C₁₋₆ alkyl optionally substituted with one or more OH, halo, or —CN, c) —(CH₂)_(q)-aryl, d) —CO₂R₄₀, e) —COR₄₁, f) —C(═O)—(CH₂)_(q)—C(═O)R₄₀, g) —S(═O)₂—C₁₋₆ alkyl, h) —S(═O)₂—(CH₂)_(q)-aryl, or i) —(C═O)_(j)-Het; R₄₀ is a) H, b) C₁₋₆ alkyl optionally substituted with one or more OH, halo, or —CN, c) —(CH₂)_(q)-aryl, or d) —(CH₂)_(q)—OR₄₂; R₄₁ is a) C₁₋₆ alkyl optionally substituted with one or more OH, halo, or —CN, b) —(CH₂)_(q)-aryl, or c) —(CH₂)_(q)—OR₄₂; R₄₂ is a) H, b) C₁₋₆ alkyl, c) —(CH₂)_(q)-aryl, or d) —C(═O)—C₁₋₆ alkyl; aryl is a) phenyl, b) pyridyl, or c) napthyl; a to c optionally substituted with one or more halo, —CN, OH, SH, C₁₋₆ alkyl, C₁₋₆ alkoxy, or C₁₋₆ alkylthio; h is 1, 2, or 3; i is 0, 1, or 2; j is 0 or 1, with the proviso that when j is 0, Y₂ is —CH₂—; k is 3, 4, or 5; l is 2 or 3; m is 4 or 5; n is 0, 1, 2, 3, 4, or 5; p is 0, 1, 2, 3, 4, or 5; with the proviso that n and p together are 1, 2, 3, 4, or 5; q is 1, 2, 3, or 4; u is 1 or 2; w is 0, 1, 2, or 3; x is 0, 1, 2, 3 or 4; and y is 0, 1, 2, 3 or 4; with the proviso that x and y taken together are 3 or 4; z is 1, 2, 3, 4 or 5, provided that i and z taken together are 2, 3, 4 or
 5. 19. The method of claim 18, wherein G is

 and A is


20. The method of claim 19, wherein R₂₃ and R₂₄ are each independently H or F and Q is selected from the group consisting of


21. The method of claim 15, wherein R₂₃ and R₂₄ are each independently H or F and Q is selected from the group consisting of


22. The method of claim 15, wherein Q is

Q and R₂₄ taken together are

wherein A² is a) H—, b) HO—, c) CH₃—, d) CH₃₀—, e) P 102O—CH₂—C(O)—NH— f) R¹⁰³O—C(O)—NH—, g) (C₁-C₂)alkyl-O—C(O)—, h) HO—CH₂—, i) CH₃O—NH—, j) (C₁-C₃)alkyl-O₂C— k) CH₃—C(O)—, or l) CH₃—C(O)—CH₂—; wherein R¹⁰⁶ is a) CH₃—C(O)—, b) H—C(O)—, c) Cl₂CH—C(O)—, d) HOCH₂—C(O)—, e) CH₃SO₂—, g) F2CHC(O)—, i) H₃C—C(O)—O—CH₂—C(O)—, j) H—C(O)—O—CH₂—C(O)—, l) HC≡C—CH₂O—CH₂—C(O)—, or m) phenyl-CH₂—O—CH₂—C(O)—; wherein R¹⁰⁷ is a) R¹⁰²O—C(R¹¹⁰)(R¹¹¹)—C(O)—, b) R¹⁰³O—C(O)—, c) R¹⁰⁸—C(O)—, f) H₃C—C(O)—(CH₂)₂—C(O)—, g) R¹⁰⁹—SO₂—, i) HO—CH₂—C(O)—, j) R¹¹⁶—(CH₂)₂—, k) R¹¹³—C (O)—O—CH₂—C(O)— l) (CH₃)₂N—CH₂—C(O)—NH—, m) NC—CH₂—, n) F₂—CH—CH₂—, or o) R¹⁵⁰R¹⁵¹NSO₂ p) C(O)CR₁₈₀R₁₈₀R₁₈₁OR₁₈₂, q) C(O)CH₂S(O)CH₃, r) C(O)CH₂S(O)(NR₁₈₃)CH₃, s) C(S)R₁₈₄, t) C(O)CH₂OR₁₈₅, u) C(O)(CH₂)_(j)C(O)CH₃, v) C(O)(CH₂OH)₂CH₃, w) C(O)CH₂CH₂OR₁₈₉, or x) —CN.
 23. The method of claim 18, wherein Q is

Q and R₂₄ taken together are

wherein A is a) H—, b) HO—, c) CH₃—, d) CH₃O—, e) R¹⁰²O—CH₂—C(O)—NH— f) R¹⁰³O—C(O)—NH—, g) (C₁-C₂)alkyl-O—C(O) h) HO—CH₂—, i) CH₃O—NH—, j) (C₁-C₃)alkyl-O₂C— k) CH₃—C(O)—, or l) CH₃—C(O)—CH₂—; wherein R¹⁰⁶ is a) CH₃—C(O)—, b) H—C(O)—, c) Cl₂CH—C(O)—, d) HOCH₂—C(O)—, e) CH₃SO₂—, g) F2CHC(O)—, i) H₃C—C(O)—O—CH₂—C(O)—, j) H—C(O)—O—CH₂—C(O)—, l) HC≡C—CH₂O—CH₂—C(O)—, or m) phenyl-CH₂—O—CH₂—C(O)— wherein R¹⁰⁷ is a) R¹⁰²O—C(R¹¹⁰)(R¹¹¹)—C(O)—, b) R¹⁰³O—C(O) c) R¹⁰⁸—C(O)—, f) H₃C—C(O)—(CH₂)₂—C(O)—, g) R¹⁰⁹—SO₂—, i) HO—CH₂—C(O)—, j) R¹¹⁶—(CH₂)₂—, k) R¹¹³—C(O)—O—CH₂—C(O)— l) (CH₃)₂N—CH₂—C(O)—NH—, m) NC—CH₂—, n) F₂—CH—CH₂—, or o) R¹⁵⁰R¹⁵¹NSO₂ p) C(O)CR₁₈₀R₁₈₀R₁₈₁OR₁₈₂, q) C(O)CH₂S(O)_(i)CH₃, r) C(O)CH₂S(O)(NR₁₈₃)CH₃, s) C(S)R₁₈₄, t) C(O)CH₂OR₁₈₅, u) C(O)(CH₂)_(j)C(O)CH₃, v) C(O)(CH₂OH)₂CH₃, w) C(O)CH₂CH₂OR₁₈₉, or x) —CN. 